48 results on '"matrikines"'
Search Results
2. Cancer Stem Cells Niche Regulation Within the Tumor Microenvironment
- Author
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Siddiqui, Zainab, Equbal, Zaffar, Muhammad, Naoshad, Usmani, Darksha, Sankhwar, Satya N., Rizvi, S. Nishat Fatima, and Naeem, Abdul
- Published
- 2024
- Full Text
- View/download PDF
3. Collagens and Collagen-Degrading Enzymes in the Regulation of Angiogenesis
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Kanellopoulou, Vasiliki Κ., Xanthopoulos, Athanasios, Mikelis, Constantinos Marios, Papadimitriou, Evangelia, Karamanos, Nikos K., Series Editor, Kletsas, Dimitris, Editorial Board Member, Oh, Eok-Soo, Editorial Board Member, Passi, Alberto, Editorial Board Member, Pihlajaniemi, Taina, Editorial Board Member, Ricard-Blum, Sylvie, Editorial Board Member, Sagi, Irit, Editorial Board Member, Savani, Rashmin, Editorial Board Member, Watanabe, Hideto, Editorial Board Member, Papadimitriou, Evangelia, editor, and Mikelis, Constantinos M., editor
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- 2023
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4. Basement membrane product, endostatin, as a link between inflammation, coagulation and vascular permeability in COVID-19 and non-COVID-19 acute respiratory distress syndrome.
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Jandl, Katharina, Berg, Johannes Lorenz, Birnhuber, Anna, Fliesser, Elisabeth, Borek, Izabela, Seeliger, Benjamin, David, Sascha, Schmidt, Julius J., Gorkiewicz, Gregor, Zacharias, Martin, Welte, Tobias, Olschewski, Horst, Heinemann, Akos, Wygrecka, Malgorzata, and Kwapiszewska, Grazyna
- Subjects
ADULT respiratory distress syndrome ,ENDOSTATIN ,BASAL lamina ,COVID-19 ,BLOOD platelet aggregation - Abstract
Background: Immune cell recruitment, endothelial cell barrier disruption, and platelet activation are hallmarks of lung injuries caused by COVID-19 or other insults which can result in acute respiratory distress syndrome (ARDS). Basement membrane (BM) disruption is commonly observed in ARDS, however, the role of newly generated bioactive BM fragments is mostly unknown. Here, we investigate the role of endostatin, a fragment of the BM protein collagen XVIIIa1, on ARDS associated cellular functions such as neutrophil recruitment, endothelial cell barrier integrity, and platelet aggregation in vitro. Methods: In our study we analyzed endostatin in plasma and post-mortem lung specimens of patients with COVID-19 and non-COVID-19 ARDS. Functionally, we investigated the effect of endostatin on neutrophil activation and migration, platelet aggregation, and endothelial barrier function in vitro. Additionally, we performed correlation analysis for endostatin and other critical plasma parameters. Results: We observed increased plasma levels of endostatin in our COVID-19 and non-COVID-19 ARDS cohort. Immunohistochemical staining of ARDS lung sections depicted BM disruption, alongside immunoreactivity for endostatin in proximity to immune cells, endothelial cells, and fibrinous clots. Functionally, endostatin enhanced the activity of neutrophils, and platelets, and the thrombininduced microvascular barrier disruption. Finally, we showed a positive correlation of endostatin with soluble disease markers VE-Cadherin, c-reactive protein (CRP), fibrinogen, and interleukin (IL)-6 in our COVID-19 cohort. Conclusion: The cumulative effects of endostatin on propagating neutrophil chemotaxis, platelet aggregation, and endothelial cell barrier disruption may suggest endostatin as a link between those cellular events in ARDS pathology. [ABSTRACT FROM AUTHOR]
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- 2023
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- View/download PDF
5. Current Insights into the Formulation and Delivery of Therapeutic and Cosmeceutical Agents for Aging Skin.
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Altay Benetti, Ayça, Tarbox, Tamara, and Benetti, Camillo
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COSMETICS ,SKIN aging ,COMMERCIAL products ,NANOPARTICLES ,PEPTIDES - Abstract
"Successful aging" counters the traditional idea of aging as a disease and is increasingly equated with minimizing age signs on the skin, face, and body. From this stems the interest in preventative aesthetic dermatology that might help with the healthy aging of skin, help treat or prevent certain cutaneous disorders, such as skin cancer, and help delay skin aging by combining local and systemic methods of therapy, instrumental devices, and invasive procedures. This review will discuss the main mechanisms of skin aging and the potential mechanisms of action for commercial products already on the market, highlighting the issues related to the permeation of the skin from different classes of compounds, the site of action, and the techniques employed to overcome aging. The purpose is to give an overall perspective on the main challenges in formulation development, especially nanoparticle formulations, which aims to defeat or slow down skin aging, and to highlight new market segments, such as matrikines and matrikine-like peptides. In conclusion, by applying enabling technologies such as those delivery systems outlined here, existing agents can be repurposed or fine-tuned, and traditional but unproven treatments can be optimized for efficacious dosing and safety. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
6. Versican in Tumor Progression, Tumor–Host Interactions, and Cancer Immunotherapy
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Papadas, Athanasios, Cicala, Alexander, Kraus, Sean G., Arauz, Garrett, Tong, Alexander, Deming, Dustin, Asimakopoulos, Fotis, Karamanos, Nikos K., Series Editor, Kletsas, Dimitris, Editorial Board Member, Oh, Eok-Soo, Editorial Board Member, Passi, Alberto, Editorial Board Member, Pihlajaniemi, Taina, Editorial Board Member, Ricard-Blum, Sylvie, Editorial Board Member, Sagi, Irit, Editorial Board Member, Savani, Rashmin, Editorial Board Member, Watanabe, Hideto, Editorial Board Member, Kovalszky, Ilona, editor, Franchi, Marco, editor, and Alaniz, Laura D., editor
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- 2022
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7. Basement membrane product, endostatin, as a link between inflammation, coagulation and vascular permeability in COVID-19 and non-COVID-19 acute respiratory distress syndrome
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Katharina Jandl, Johannes Lorenz Berg, Anna Birnhuber, Elisabeth Fliesser, Izabela Borek, Benjamin Seeliger, Sascha David, Julius J. Schmidt, Gregor Gorkiewicz, Martin Zacharias, Tobias Welte, Horst Olschewski, Akos Heinemann, Malgorzata Wygrecka, and Grazyna Kwapiszewska
- Subjects
extracellular matrix ,matrikines ,acute lung injury ,neutrophils ,endothelium ,platelets ,Immunologic diseases. Allergy ,RC581-607 - Abstract
BackgroundImmune cell recruitment, endothelial cell barrier disruption, and platelet activation are hallmarks of lung injuries caused by COVID-19 or other insults which can result in acute respiratory distress syndrome (ARDS). Basement membrane (BM) disruption is commonly observed in ARDS, however, the role of newly generated bioactive BM fragments is mostly unknown. Here, we investigate the role of endostatin, a fragment of the BM protein collagen XVIIIα1, on ARDS associated cellular functions such as neutrophil recruitment, endothelial cell barrier integrity, and platelet aggregation in vitro.MethodsIn our study we analyzed endostatin in plasma and post-mortem lung specimens of patients with COVID-19 and non-COVID-19 ARDS. Functionally, we investigated the effect of endostatin on neutrophil activation and migration, platelet aggregation, and endothelial barrier function in vitro. Additionally, we performed correlation analysis for endostatin and other critical plasma parameters.ResultsWe observed increased plasma levels of endostatin in our COVID-19 and non-COVID-19 ARDS cohort. Immunohistochemical staining of ARDS lung sections depicted BM disruption, alongside immunoreactivity for endostatin in proximity to immune cells, endothelial cells, and fibrinous clots. Functionally, endostatin enhanced the activity of neutrophils, and platelets, and the thrombin-induced microvascular barrier disruption. Finally, we showed a positive correlation of endostatin with soluble disease markers VE-Cadherin, c-reactive protein (CRP), fibrinogen, and interleukin (IL)-6 in our COVID-19 cohort.ConclusionThe cumulative effects of endostatin on propagating neutrophil chemotaxis, platelet aggregation, and endothelial cell barrier disruption may suggest endostatin as a link between those cellular events in ARDS pathology.
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- 2023
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8. Bioactive extracellular matrix fragments in tendon repair.
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Mohindra, Ritika, Mohindra, Rohit, Agrawal, Devendra K., and Thankam, Finosh G.
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EXTRACELLULAR matrix , *TENDONS , *BIOACTIVE glasses , *REPAIRING , *METALLOPROTEINASES , *TENDINOPATHY ,TENDON injury healing - Abstract
Tendinopathy is a common tendon disorder that causes pain, loss of strength and function, and local inflammation mainly characterized by hypoxia, collagen degradation, and extracellular matrix (ECM) disorganization. Generally, ECM degradation and remodeling is tightly regulated; however, hyperactivation of matrix metalloproteases (MMPs) contributes to excessive collagenolysis under pathologic conditions resulting in tendon ECM degradation. This review article focuses on the production, function, and signaling of matrikines for tendon regeneration following injury with insights into the expression, tissue compliance, and cell proliferation exhibited by various matrikines. Furthermore, the regenerative properties suggest translational significance of matrikines to improve the outcomes post-injury by assisting with tendon healing. [ABSTRACT FROM AUTHOR]
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- 2022
- Full Text
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9. Development of Matrix Metalloproteinases-Mediated Extracellular Matrix Remodeling in Regenerative Medicine: A Mini Review
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Chen, Kaiqi, Xu, Mimi, Lu, Feng, and He, Yunfan
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- 2023
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10. The role of network‐forming collagens in cancer progression.
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Zhang, Jin, Liu, Jieya, Zhang, Hongying, Wang, Jiao, Hua, Hui, and Jiang, Yangfu
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CANCER invasiveness ,COLLAGEN ,EXTRACELLULAR matrix ,TUMOR microenvironment ,CELL proliferation - Abstract
Collagens are the main components of extracellular matrix in the tumor microenvironment. Both fibrillar and nonfibrillar collagens are involved in tumor progression. The nonfibrillar network‐forming collagens such as type IV and type VIII collagens are frequently overexpressed in various types of human cancers, which promotes tumor cell proliferation, adhesion, invasion, metastasis and angiogenesis. Studies on the roles of these collagens have shed light on the mechanisms underpinning the effects of this protein family. Future research has to explicit the role of network‐forming collagens with respect to cancer progression and treatment. Herein, we review the regulation of network‐forming collagens expression in cancer; the roles of network‐forming collagens in tumor invasion, metastasis and angiogenesis; and the clinical significance of network‐forming collagens expression in cancer patients. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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11. CNS/PNS proteoglycans functionalize neuronal and astrocyte niche microenvironments optimizing cellular activity by preserving membrane polarization dynamics, ionic microenvironments, ion fluxes, neuronal activation, and network neurotransductive capacity.
- Author
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Melrose J
- Subjects
- Animals, Extracellular Matrix metabolism, Humans, Cellular Microenvironment physiology, Central Nervous System metabolism, Neuronal Plasticity physiology, Proteoglycans metabolism, Neurons metabolism, Astrocytes metabolism
- Abstract
Central and peripheral nervous system (CNS/PNS) proteoglycans (PGs) have diverse functional roles, this study examined how these control cellular behavior and tissue function. The CNS/PNS extracellular matrix (ECM) is a dynamic, responsive, highly interactive, space-filling, cell supportive, stabilizing structure maintaining tissue compartments, ionic microenvironments, and microgradients that regulate neuronal activity and maintain the neuron in an optimal ionic microenvironment. The CNS/PNS contains a high glycosaminoglycan content (60% hyaluronan, HA) and a diverse range of stabilizing PGs. Immobilization of HA in brain tissues by HA interactive hyalectan PGs preserves tissue hydration and neuronal activity, a paucity of HA in brain tissues results in a pro-convulsant epileptic phenotype. Diverse CS, KS, and HSPGs stabilize the blood-brain barrier and neurovascular unit, provide smart gel neurotransmitter neuron vesicle storage and delivery, organize the neuromuscular junction basement membrane, and provide motor neuron synaptic plasticity, and photoreceptor and neuron synaptic functions. PG-HA networks maintain ionic fluxes and microgradients and tissue compartments that contribute to membrane polarization dynamics essential to neuronal activation and neurotransduction. Hyalectans form neuroprotective perineuronal nets contributing to synaptic plasticity, memory, and cognitive learning. Sialoglycoprotein associated with cones and rods (SPACRCAN), an HA binding CSPG, stabilizes the inter-photoreceptor ECM. HSPGs pikachurin and eyes shut stabilize the photoreceptor synapse aiding in phototransduction and neurotransduction with retinal bipolar neurons crucial to visual acuity. This is achieved through Laminin G motifs in pikachurin, eyes shut, and neurexins that interact with the dystroglycan-cytoskeleton-ECM-stabilizing synaptic interconnections, neuronal interactive specificity, and co-ordination of regulatory action potentials in neural networks., (© 2024 The Author(s). Journal of Neuroscience Research published by Wiley Periodicals LLC.)
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- 2024
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12. Current Insights into the Formulation and Delivery of Therapeutic and Cosmeceutical Agents for Aging Skin
- Author
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Ayça Altay Benetti, Tamara Tarbox, and Camillo Benetti
- Subjects
skin aging ,microneedle ,matrikines ,peptides ,cosmetics ,SLNs ,Chemistry ,QD1-999 - Abstract
“Successful aging” counters the traditional idea of aging as a disease and is increasingly equated with minimizing age signs on the skin, face, and body. From this stems the interest in preventative aesthetic dermatology that might help with the healthy aging of skin, help treat or prevent certain cutaneous disorders, such as skin cancer, and help delay skin aging by combining local and systemic methods of therapy, instrumental devices, and invasive procedures. This review will discuss the main mechanisms of skin aging and the potential mechanisms of action for commercial products already on the market, highlighting the issues related to the permeation of the skin from different classes of compounds, the site of action, and the techniques employed to overcome aging. The purpose is to give an overall perspective on the main challenges in formulation development, especially nanoparticle formulations, which aims to defeat or slow down skin aging, and to highlight new market segments, such as matrikines and matrikine-like peptides. In conclusion, by applying enabling technologies such as those delivery systems outlined here, existing agents can be repurposed or fine-tuned, and traditional but unproven treatments can be optimized for efficacious dosing and safety.
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- 2023
- Full Text
- View/download PDF
13. The basement membrane in the cross-roads between the lung and kidney.
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Jandl, Katharina, Mutgan, Ayse Ceren, Eller, Kathrin, Schaefer, Liliana, and Kwapiszewska, Grazyna
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BASAL lamina , *LUNGS , *VASCULAR endothelium , *KIDNEYS , *CHRONIC kidney failure , *LUNG diseases - Abstract
• The BM in the lung and the kidney are similar in composition and structure. • Ultrastructural changes underlie both acute and chronic lung and kidney diseases, often with prominent BM thickening that can even precede inflammatory responses. • Full length BM proteins and their proteolytic fragments can serve as potential biomarkers in lung and kidney diseases, but also actively contribute to disease progression. • Circulating BM components can be involved in mediating the pulmonary-renal interaction axis. The basement membrane (BM) is a specialized layer of extracellular matrix components that plays a central role in maintaining lung and kidney functions. Although the composition of the BM is usually tissue specific, the lung and the kidney preferentially use similar BM components. Unsurprisingly, diseases with BM defects often have severe pulmonary or renal manifestations, sometimes both. Excessive remodeling of the BM, which is a hallmark of both inflammatory and fibrosing diseases in the lung and the kidney, can lead to the release of BM-derived matrikines, proteolytic fragments with distinct biological functions. These matrikines can then influence disease activity at the site of liberation. However, they are also released to the circulation, where they can directly affect the vascular endothelium or target other organs, leading to extrapulmonary or extrarenal manifestations. In this review, we will summarize the current knowledge of the composition and function of the BM and its matrikines in health and disease, both in the lung and in the kidney. By comparison, we will highlight, why the BM and its matrikines may be central in establishing a renal-pulmonary interaction axis. [ABSTRACT FROM AUTHOR]
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- 2022
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14. Pulmonary Matrikines: Origin, Function, and Contribution to Fibrotic and Non-fibrotic Lung Disease
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George, Gautam, Walker, Janice, Summer, Ross, Coleman, William B., Series Editor, Tsongalis, Gregory J., Series Editor, Willis, Monte S., editor, Yates, Cecelia C., editor, and Schisler, Jonathan C., editor
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- 2019
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15. Altered Vascular Extracellular Matrix in the Pathogenesis of Atherosclerosis.
- Author
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Mohindra, Rohit, Agrawal, Devendra K., and Thankam, Finosh G.
- Abstract
Cardiovascular disease continues to grow as a massive global health burden, with coronary artery disease being one of its most lethal varieties. The pathogenesis of atherosclerosis induces changes in the blood vessel and its extracellular matrix (ECM) in each vascular layer. The alteration of the ECM homeostasis has significant modulatory effects on the inflammatory response, the proliferation and migration of vascular smooth muscle cells, neointimal formation, and vascular fibrosis seen in atherosclerosis. In this literature review, the role of the ECM, the multitude of components, and alterations to these components in the pathogenesis of atherosclerosis are discussed with a focus on versatile cellular phenotypes in the structure of blood vessel. An understanding of the various effects of ECM alterations opens up a plethora of therapeutic options that would mitigate the substantial health toll of atherosclerosis on the global population. [ABSTRACT FROM AUTHOR]
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- 2021
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16. The Functional Role of Extracellular Matrix Proteins in Cancer
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Nadezhda V. Popova and Manfred Jücker
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extracellular matrix ,tumor microenvironment ,tumor progression ,matrix metalloproteinases ,matrikines ,tenascin ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
The extracellular matrix (ECM) is highly dynamic as it is constantly deposited, remodeled and degraded to maintain tissue homeostasis. ECM is a major structural component of the tumor microenvironment, and cancer development and progression require its extensive reorganization. Cancerized ECM is biochemically different in its composition and is stiffer compared to normal ECM. The abnormal ECM affects cancer progression by directly promoting cell proliferation, survival, migration and differentiation. The restructured extracellular matrix and its degradation fragments (matrikines) also modulate the signaling cascades mediated by the interaction with cell-surface receptors, deregulate the stromal cell behavior and lead to emergence of an oncogenic microenvironment. Here, we summarize the current state of understanding how the composition and structure of ECM changes during cancer progression. We also describe the functional role of key proteins, especially tenascin C and fibronectin, and signaling molecules involved in the formation of the tumor microenvironment, as well as the signaling pathways that they activate in cancer cells.
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- 2022
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17. Versican and Versican-matrikines in Cancer Progression, Inflammation, and Immunity.
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Papadas, Athanasios, Arauz, Garrett, Cicala, Alexander, Wiesner, Joshua, and Asimakopoulos, Fotis
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CANCER invasiveness ,VERSICAN ,EXTRACELLULAR matrix ,PROTEOGLYCANS ,IMMUNE response ,IMMUNOTHERAPY - Abstract
Versican is an extracellular matrix proteoglycan with key roles in multiple facets of cancer development, ranging from proliferative signaling, evasion of growth-suppressor pathways, regulation of cell death, promotion of neoangiogenesis, and tissue invasion and metastasis. Multiple lines of evidence implicate versican and its bioactive proteolytic fragments (matrikines) in the regulation of cancer inflammation and antitumor immune responses. The understanding of the dynamics of versican deposition/accumulation and its proteolytic turnover holds potential for the development of novel immune biomarkers as well as approaches to reset the immune thermostat of tumors, thus promoting efficacy of modern immunotherapies. This article summarizes work from several laboratories, including ours, on the role of this central matrix proteoglycan in tumor progression as well as tumor-immune cell cross-talk: [ABSTRACT FROM AUTHOR]
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- 2020
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18. Tumor Microenvironment: Extracellular Matrix Alterations Influence Tumor Progression
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Sylvie Brassart-Pasco, Stéphane Brézillon, Bertrand Brassart, Laurent Ramont, Jean-Baptiste Oudart, and Jean Claude Monboisse
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cancer ,microenvironment ,extracellular matrix ,matrikines ,integrins ,proteases ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
The tumor microenvironment (TME) is composed of various cell types embedded in an altered extracellular matrix (ECM). ECM not only serves as a support for tumor cell but also regulates cell–cell or cell–matrix cross-talks. Alterations in ECM may be induced by hypoxia and acidosis, by oxygen free radicals generated by infiltrating inflammatory cells or by tumor- or stromal cell-secreted proteases. A poorer diagnosis for patients is often associated with ECM alterations. Tumor ECM proteome, also named cancer matrisome, is strongly altered, and different ECM protein signatures may be defined to serve as prognostic biomarkers. Collagen network reorganization facilitates tumor cell invasion. Proteoglycan expression and location are modified in the TME and affect cell invasion and metastatic dissemination. ECM macromolecule degradation by proteases may induce the release of angiogenic growth factors but also the release of proteoglycan-derived or ECM protein fragments, named matrikines or matricryptins. This review will focus on current knowledge and new insights in ECM alterations, degradation, and reticulation through cross-linking enzymes and on the role of ECM fragments in the control of cancer progression and their potential use as biomarkers in cancer diagnosis and prognosis.
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- 2020
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19. Tumor Microenvironment: Extracellular Matrix Alterations Influence Tumor Progression.
- Author
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Brassart-Pasco, Sylvie, Brézillon, Stéphane, Brassart, Bertrand, Ramont, Laurent, Oudart, Jean-Baptiste, and Monboisse, Jean Claude
- Subjects
EXTRACELLULAR matrix ,TUMOR microenvironment ,CANCER invasiveness ,REACTIVE oxygen species ,VASCULAR endothelial growth factors - Abstract
The tumor microenvironment (TME) is composed of various cell types embedded in an altered extracellular matrix (ECM). ECM not only serves as a support for tumor cell but also regulates cell–cell or cell–matrix cross-talks. Alterations in ECM may be induced by hypoxia and acidosis, by oxygen free radicals generated by infiltrating inflammatory cells or by tumor- or stromal cell-secreted proteases. A poorer diagnosis for patients is often associated with ECM alterations. Tumor ECM proteome, also named cancer matrisome, is strongly altered, and different ECM protein signatures may be defined to serve as prognostic biomarkers. Collagen network reorganization facilitates tumor cell invasion. Proteoglycan expression and location are modified in the TME and affect cell invasion and metastatic dissemination. ECM macromolecule degradation by proteases may induce the release of angiogenic growth factors but also the release of proteoglycan-derived or ECM protein fragments, named matrikines or matricryptins. This review will focus on current knowledge and new insights in ECM alterations, degradation, and reticulation through cross-linking enzymes and on the role of ECM fragments in the control of cancer progression and their potential use as biomarkers in cancer diagnosis and prognosis. [ABSTRACT FROM AUTHOR]
- Published
- 2020
- Full Text
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20. Proline‐containing peptides—New insight and implications: A Review.
- Author
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Misiura, Magdalena and Miltyk, Wojciech
- Subjects
- *
SOMATOMEDIN , *INTESTINAL ischemia , *MOLECULAR pathology , *GASTRIC mucosa , *PARKINSON'S disease , *PROTEOLYSIS - Abstract
The family of regulatory proline‐containing peptides (PCPs), also known as glyprolines, exhibit significant biological activity. The group of glyprolines includes Gly‐Pro (GP), Pro‐Gly‐Pro (PGP), cyclic Gly‐Pro (cGP), as well as PGP derivatives, for example, N‐acetylated PGP (N‐a‐PGP) and N‐methylated PGP (N‐m‐PGP). PCPs are engaged in various biological processes including the proinflammatory neutrophil chemoattraction in lung diseases, inflammatory bowel diseases or ischemic stroke. Glyprolines have been also postulated to play an important role as atheroprotective and anticoagulant agents, exhibit neuroprotective effects in Parkinson's disease, as well as regulate insulin‐like growth factor (IGF) homeostasis. It was also noticed that PCPs inhibit proliferation and migration of keratinocytes in wound healing, protection of the gastric mucosa and stimulation of its regeneration. The regulatory glyprolines are derived from endogenous and exogenous sources. Most PCPs are derived from collagen or diet protein degradation. Recently, great interest is concentrated on short proline‐rich oligopeptides derived from IGF‐1 degradation. The mechanism of PCPs biological activity is not fully explained. It involves receptor‐mediated mechanisms, for example, N‐a‐PGP acts as CXCR1/2 receptor ligand, whereas cGP regulates IGF‐1 bioavailability by modifying the IGF‐1 binding to the IGF‐1 binding protein‐3. PGP has been observed to interact with collagen‐specific receptors. The data suggest a promising role of PGP as a target of various diseases therapy. This review is focused on the effect of PCPs on metabolic processes in different tissues and the molecular mechanism of their action as an approach to pharmacotherapy of PCPs‐dependent diseases. [ABSTRACT FROM AUTHOR]
- Published
- 2019
- Full Text
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21. The Multi-Faceted Extracellular Matrix: Unlocking Its Secrets for Understanding the Perpetuation of Lung Fibrosis
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Nizamoglu, Mehmet and Burgess, Janette K.
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- 2021
- Full Text
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22. Fragments generated upon extracellular matrix remodeling: Biological regulators and potential drugs.
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Ricard-Blum, Sylvie and Vallet, Sylvain D.
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PROTEOLYTIC enzymes , *EXTRACELLULAR matrix , *BIOACTIVE compounds , *PROTEINASES , *GENE expression , *CELL communication - Abstract
Abstract The remodeling of the extracellular matrix (ECM) by several protease families releases a number of bioactive fragments, which regulate numerous biological processes such as autophagy, angiogenesis, adipogenesis, fibrosis, tumor growth, metastasis and wound healing. We review here the proteases which generate bioactive ECM fragments, their ECM substrates, the major bioactive ECM fragments, together with their biological properties and their receptors. The translation of ECM fragments into drugs is challenging and would take advantage of an integrative approach to optimize the design of pre-clinical and clinical studies. This could be done by building the contextualized interaction network of the ECM fragment repertoire including their parent proteins, remodeling proteinases, and their receptors, and by using mathematical disease models. Highlights • Zinc, serine or cysteine proteases release ECM bioactive fragments during ECM remodeling. • Bioactive ECM fragments regulate major biological processes (e.g. angiogenesis, tumor growth, fibrosis, and adipogenesis). • Different ECM fragments may regulate the same biological process. • ECM fragments modulate gene expression, cell signaling and enzyme activation/activity. • ECM fragments are potential drugs and are diagnostic and prognostic markers of diseases. [ABSTRACT FROM AUTHOR]
- Published
- 2019
- Full Text
- View/download PDF
23. Matrikines for therapeutic and biomedical applications.
- Author
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Sivaraman, K. and Shanthi, C.
- Subjects
- *
PEPTIDES , *EXTRACELLULAR matrix proteins , *BIOACTIVE compounds , *APOPTOSIS , *CELL differentiation - Abstract
Abstract Matrikines, peptides originating from the fragmentation of extracellular matrix proteins are identified to play important role in both health and disease. They possess biological activities, much different from their parent protein. Identification of such bioactive cryptic regions in the extracellular matrix proteins has attracted the researchers all over the world in the recent decade. These bioactive peptides could find use in preparation of biomaterials and tissue engineering applications. Matrikines identified in major extracellular matrix (ECM) proteins like collagen, elastin, fibronectin, and laminin are being extensively studied for use in tissue engineering and regenerative medicine. They are identified to modulate cellular activity like cell growth, proliferation, migration and may induce apoptosis. RGD, a well-known peptide identified in fibronectin with cell adhesive property is being investigated in designing biomaterials. Collagen hexapeptide GFOGER was found to promote cell adhesion and differentiation. Laminin also possesses regions with strong cell adhesion property. Recently, cell-penetrating peptides from elastin are used as a targeted delivery system for therapeutic drugs. The continued search for cryptic sequences in the extracellular matrix proteins along with advanced peptide coupling chemistries would lead to biomaterials with improved surface properties. This review article outlines the peptides derived from extracellular matrix and some of the possible applications of these peptides in therapeutics and tissue engineering applications. Graphical abstract Unlabelled Image [ABSTRACT FROM AUTHOR]
- Published
- 2018
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24. Hold on or Cut? Integrin- and MMP-Mediated Cell–Matrix Interactions in the Tumor Microenvironment
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Stephan Niland and Johannes A. Eble
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tumor microenvironment ,extracellular matrix ,integrins ,matrix metalloproteinases ,matrikines ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
The tumor microenvironment (TME) has become the focus of interest in cancer research and treatment. It includes the extracellular matrix (ECM) and ECM-modifying enzymes that are secreted by cancer and neighboring cells. The ECM serves both to anchor the tumor cells embedded in it and as a means of communication between the various cellular and non-cellular components of the TME. The cells of the TME modify their surrounding cancer-characteristic ECM. This in turn provides feedback to them via cellular receptors, thereby regulating, together with cytokines and exosomes, differentiation processes as well as tumor progression and spread. Matrix remodeling is accomplished by altering the repertoire of ECM components and by biophysical changes in stiffness and tension caused by ECM-crosslinking and ECM-degrading enzymes, in particular matrix metalloproteinases (MMPs). These can degrade ECM barriers or, by partial proteolysis, release soluble ECM fragments called matrikines, which influence cells inside and outside the TME. This review examines the changes in the ECM of the TME and the interaction between cells and the ECM, with a particular focus on MMPs.
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- 2020
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25. LC-MS/MS method for proline-glycine-proline and acetylated proline-glycine-proline in human plasma.
- Author
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Tiwary, Ekta, Berryhill, Taylor F, Wilson, Landon, Barnes, Stephen, Prasain, Jeevan K, and Wells, J Michael
- Subjects
- *
LIQUID chromatography-mass spectrometry , *MATRIX metalloproteinases , *MATRIX effect , *ELASTIN , *FREEZE-thaw cycles , *ELASTASES , *GLYCINE receptors , *NEPRILYSIN - Abstract
The extracellular cellular matrix (ECM) maintains tissue structure and regulates signaling functions by continuous degradation and remodeling. Inflammation or other disease conditions activate proteases including matrix metalloproteinases (MMPs) that degrade ECM proteins and in particular generate fragments of collagen and elastin, some of which are biologically active ECM peptides or matrikines. Stepwise degradation of collagen by MMP 8, 9 and prolyl endopeptidase release the matrikine proline-glycine-proline (PGP) and its product acetyl-PGP (AcPGP). These peptides are considered as potential biomarkers and therapeutic targets for many disease conditions such as chronic lung disease, heart disease, and cancer. However, there is no published, validated method for the measurement of PGP and AcPGP in plasma and therefore, we developed a sensitive, selective and reliable, isotope dilution LC-multiple reaction monitoring MS method for their determination in human plasma. The chromatographic separation of PGP and AcPGP was achieved in 3 min using Jupiter column with a gradient consisting of acidified acetonitrile and water at a flow rate of 0.5 ml/min. The limit of detection (LOD) for PGP and AcPGP was 0.01 ng/ml and the limit of quantification (LOQ) was 0.05 ng/ml and 0.1 ng/ml, respectively. Precision and accuracy values for all analytes were within 20 % except for the lowest QC of 0.01 ng/ml. The mean extraction recoveries of these analytes were > 90 % using a Phenomenex Phree cartridge and the matrix effect was < 15 % for all the QCs for PGP and AcPGP except the lowest QC. The stability of PGP and AcPGP was > 90 % in several tested conditions including autosampler use, storage at −80 °C, and after 6 times freeze–thaw cycles. Using this method, we successfully extracted and determined PGP levels in human plasma from healthy and COPD subjects. Therefore, this method is suitable for quantification of these peptides in the clinical setting. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
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26. Endothelial Basement Membrane Components and Their Products, Matrikines: Active Drivers of Pulmonary Hypertension?
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Ayse Ceren Mutgan, Katharina Jandl, and Grazyna Kwapiszewska
- Subjects
IPAH ,vascular remodeling ,basement membrane ,laminin ,type IV collagen ,matrikines ,Cytology ,QH573-671 - Abstract
Pulmonary arterial hypertension (PAH) is a vascular disease that is characterized by elevated pulmonary arterial pressure (PAP) due to progressive vascular remodeling. Extracellular matrix (ECM) deposition in pulmonary arteries (PA) is one of the key features of vascular remodeling. Emerging evidence indicates that the basement membrane (BM), a specialized cluster of ECM proteins underlying the endothelium, may be actively involved in the progression of vascular remodeling. The BM and its steady turnover are pivotal for maintaining appropriate vascular functions. However, the pathologically elevated turnover of BM components leads to an increased release of biologically active short fragments, which are called matrikines. Both BM components and their matrikines can interfere with pivotal biological processes, such as survival, proliferation, adhesion, and migration and thus may actively contribute to endothelial dysfunction. Therefore, in this review, we summarize the emerging role of the BM and its matrikines on the vascular endothelium and further discuss its implications on lung vascular remodeling in pulmonary hypertension.
- Published
- 2020
- Full Text
- View/download PDF
27. Degradation of tropoelastin and skin elastin by neprilysin.
- Author
-
Mora Huertas, Angela C., Schmelzer, Christian E.H., Luise, Chiara, Sippl, Wolfgang, Pietzsch, Markus, Hoehenwarter, Wolfgang, and Heinz, Andrea
- Subjects
- *
TROPOELASTIN , *ELASTIN , *NEPRILYSIN , *PROTEIN precursors , *CELL proliferation - Abstract
Neprilysin is also known as skin fibroblast-derived elastase, and its up-regulation during aging is associated with impairments of the elastic fiber network, loss of skin elasticity and wrinkle formation. However, information on its elastase activity is still limited. The aim of this study was to investigate the degradation of fibrillar skin elastin by neprilysin and the influence of the donor's age on the degradation process using mass spectrometry and bioinformatics approaches. The results showed that cleavage by neprilysin is dependent on previous damage of elastin. While neprilysin does not cleave young and intact skin elastin well, it degrades elastin fibers from older donors, which may further promote aging processes. With regards to the cleavage behavior of neprilysin, a strong preference for Gly at P1 was found, while Gly, Ala and Val were well accepted at P1′ upon cleavage of tropoelastin and skin elastin. The results of the study indicate that the progressive release of bioactive elastin peptides by neprilysin upon skin aging may enhance local tissue damage and accelerate extracellular matrix aging processes. [ABSTRACT FROM AUTHOR]
- Published
- 2018
- Full Text
- View/download PDF
28. Towards integrating extracellular matrix and immunological pathways.
- Author
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Boyd, David F. and Thomas, Paul G.
- Subjects
- *
EXTRACELLULAR matrix , *CYTOKINES , *MEMBRANE proteins , *GROWTH factors , *CELL migration - Abstract
The extracellular matrix (ECM) is a complex and dynamic structure made up of an estimated 300 different proteins. The ECM is also a rich source of cytokines and growth factors in addition to numerous bioactive ECM degradation products that influence cell migration, proliferation, and differentiation. The ECM is constantly being remodeled during homeostasis and in a wide range of pathological contexts. Changes in the ECM modulate immune responses, which in turn regulate repair and regeneration of tissues. Here, we review the many components of the ECM, enzymes involved in ECM remodeling, and the signals that feed into immunological pathways in the context of a dynamic ECM. We highlight studies that have taken an integrative approach to studying immune responses in the context of the ECM and studies that use novel proteomic strategies. Finally, we discuss research challenges relevant to the integration of immune and ECM networks and propose experimental and translational approaches to resolve these issues. [ABSTRACT FROM AUTHOR]
- Published
- 2017
- Full Text
- View/download PDF
29. Mesenchymal Stem Cells from Adipose Tissue in Clinical Applications for Dermatological Indications and Skin Aging.
- Author
-
Gaur, Meenakshi, Dobke, Marek, and Lunyak, Victoria V.
- Subjects
- *
TREATMENT of skin aging , *MESENCHYMAL stem cells , *SKIN regeneration , *ADIPOSE tissues , *EPIDERMIS , *HOMEOSTASIS , *THERAPEUTICS - Abstract
Operating at multiple levels of control, mesenchymal stemcells fromadipose tissue (ADSCs) communicate with organ systems to adjust immune response, provide signals for differentiation, migration, enzymatic reactions, and to equilibrate the regenerative demands of balanced tissue homeostasis. The identification of the mechanisms by which ADSCs accomplish these functions for dermatological rejuvenation and wound healing has great potential to identify novel targets for the treatment of disorders and combat aging. Herein, we review new insights into the role of adipose-derived stem cells in the maintenance of dermal and epidermal homeostasis, and recent advances in clinical applications of ADSCs related to dermatology. [ABSTRACT FROM AUTHOR]
- Published
- 2017
- Full Text
- View/download PDF
30. Cartilage extracellular matrix-derived matrikines in osteoarthritis.
- Author
-
Rapp AE and Zaucke F
- Subjects
- Humans, Extracellular Matrix metabolism, Aggrecans metabolism, Aggrecans therapeutic use, Extracellular Matrix Proteins metabolism, Chondrocytes metabolism, Cartilage, Articular metabolism, Osteoarthritis metabolism
- Abstract
Osteoarthritis (OA) is among the most frequent diseases of the musculoskeletal system. Degradation of cartilage extracellular matrix (ECM) is a hallmark of OA. During the degradation process, intact/full-length proteins and proteolytic fragments are released which then might induce different downstream responses via diverse receptors, therefore leading to different biological consequences. Collagen type II and the proteoglycan aggrecan are the most abundant components of the cartilage ECM. However, over the last decades, a large number of minor components have been identified and for some of those, a role in the manifold processes associated with OA has already been demonstrated. To date, there is still no therapy able to halt or cure OA. A better understanding of the matrikine landscape occurring with or even preceding obvious degenerative changes in joint tissues is needed and might help to identify molecules that could serve as biomarkers, druggable targets, or even be blueprints for disease modifying drug OA drugs. For this narrative review, we screened PubMed for relevant literature in the English language and summarized the current knowledge regarding the function of selected ECM molecules and the derived matrikines in the context of cartilage and OA.
- Published
- 2023
- Full Text
- View/download PDF
31. Mesenchymal Stem Cells from Adipose Tissue in Clinical Applications for Dermatological Indications and Skin Aging
- Author
-
Meenakshi Gaur, Marek Dobke, and Victoria V. Lunyak
- Subjects
adipose-derived stem cells ,skin homeostasis ,dermis ,epidermis ,subcutaneous adipose depot ,matrikines ,aging ,wound healing ,clinical applications ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
Operating at multiple levels of control, mesenchymal stem cells from adipose tissue (ADSCs) communicate with organ systems to adjust immune response, provide signals for differentiation, migration, enzymatic reactions, and to equilibrate the regenerative demands of balanced tissue homeostasis. The identification of the mechanisms by which ADSCs accomplish these functions for dermatological rejuvenation and wound healing has great potential to identify novel targets for the treatment of disorders and combat aging. Herein, we review new insights into the role of adipose-derived stem cells in the maintenance of dermal and epidermal homeostasis, and recent advances in clinical applications of ADSCs related to dermatology.
- Published
- 2017
- Full Text
- View/download PDF
32. Matrikines as mediators of tissue remodelling.
- Author
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Jariwala, Nathan, Ozols, Matiss, Bell, Mike, Bradley, Eleanor, Gilmore, Andrew, Debelle, Laurent, and Sherratt, Michael J.
- Subjects
- *
TISSUE remodeling , *PEPTIDES , *ELASTIN , *MATRIX metalloproteinases , *EXTRACELLULAR matrix - Abstract
Matrix-derived peptides may penetrate skin via multiple pathways to act on cutaneous cells. At the cellular level, the mechanisms of action of some elastin derived peptides are well known but the receptors and signalling mechanisms for other extracellular matrix peptides are yet to be established. In both panels solid lines and arrows represent known pathways, while dotted lines indicate gaps in our current understanding. Abbreviations: ERC, elastin receptor complex; Gal-3, galectin-3; ERK, extracellular signal-regulated kinase; AP-1, activator protein-1; MMP, matrix metalloproteinase; ECM, extracellular matrix. [Display omitted] Extracellular matrix (ECM) proteins confer biomechanical properties, maintain cell phenotype and mediate tissue repair (via release of sequestered cytokines and proteases). In contrast to intracellular proteomes, where proteins are monitored and replaced over short time periods, many ECM proteins function for years (decades in humans) without replacement. The longevity of abundant ECM proteins, such as collagen I and elastin, leaves them vulnerable to damage accumulation and their host organs prone to chronic, age-related diseases. However, ECM protein fragmentation can potentially produce peptide cytokines (matrikines) which may exacerbate and/or ameliorate age- and disease-related ECM remodelling. In this review, we discuss ECM composition, function and degradation and highlight examples of endogenous matrikines. We then critically and comprehensively analyse published studies of matrix-derived peptides used as topical skin treatments, before considering the potential for improvements in the discovery and delivery of novel matrix-derived peptides to skin and internal organs. From this, we conclude that while the translational impact of matrix-derived peptide therapeutics is evident, the mechanisms of action of these peptides are poorly defined. Further, well-designed, multimodal studies are required. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
33. Up-regulation of matrix metallopeptidase 12 in motor neurons undergoing synaptic stripping.
- Author
-
Sajjan, S., Holsinger, R. M. D., Fok, S., Ebrahimkhani, S., Rollo, J. L., Banati, R. B., and Graeber, M. B.
- Subjects
- *
EXTRACELLULAR matrix proteins , *MOTOR neurons , *NEUROPLASTICITY , *LABORATORY mice , *CELLULAR signal transduction , *GENE expression - Abstract
Axotomy of the rodent facial nerve represents a well-established model of synaptic plasticity. Post-traumatic "synaptic stripping" was originally discovered in this system. We report upregulation of matrix metalloproteinase MMP12 in regenerating motor neurons of the mouse and rat facial nucleus. Matrix metalloproteinases (matrix metallopeptidases, MMPs) are zinc-binding proteases capable of degrading components of the extracellular matrix and of regulating extracellular signaling networks including within synapses. MMP12 protein expression in facial motor neurons was enhanced following axotomy and peaked at day 3 after the operation. The peak of neuronal MMP12 expression preceded the peak of experimentally induced synaptic plasticity. At the same time, MMP12 redistributed intracellularly and became predominantly localized beneath the neuronal somatic cytoplasmic membrane. Both findings point to a role of MMP12 in the neuronal initiation of the synaptic stripping process. MMP12 is the first candidate molecule for such a trigger function and has potential as a therapeutic target. Moreover, since statins have been shown to increase the expression of MMP12, interference with synaptic stability may represent one mechanism by which these widely used drugs exert their side effects on higher CNS functions. [ABSTRACT FROM AUTHOR]
- Published
- 2014
- Full Text
- View/download PDF
34. Matricryptins and matrikines: biologically active fragments of the extracellular matrix.
- Author
-
Ricard‐Blum, Sylvie and Salza, Romain
- Subjects
- *
GLYCOSAMINOGLYCANS , *EXTRACELLULAR matrix proteins , *PROTEOGLYCANS , *NEURODEGENERATION , *WOUND healing , *PATHOLOGICAL physiology - Abstract
Numerous extracellular proteins and glycosaminoglycans ( GAGs) undergo limited enzymatic cleavage resulting in the release of fragments exerting biological activities, which are usually different from those of the full-length molecules. In this review, we define matrikines and matricryptins, which are bioactive fragments released from the extracellular matrix proteins, proteoglycans and GAGs and report their major biological activities. These fragments regulate a number of physiopathological processes including angiogenesis, cancer, fibrosis, inflammation, neurodegenerative diseases and wound healing. The challenges to translate these fragments from molecules biologically active in vitro and in experimental models to potential drugs are discussed in the last part of the review. [ABSTRACT FROM AUTHOR]
- Published
- 2014
- Full Text
- View/download PDF
35. Extracellular matrix and wound healing.
- Author
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Maquart, F.X. and Monboisse, J.C.
- Subjects
- *
EXTRACELLULAR matrix , *WOUND healing , *CELL proliferation , *CELL migration , *PROTEIN synthesis , *PROTEOLYSIS , *TARGETED drug delivery , *MACROMOLECULES - Abstract
Abstract: Extracellular matrix has been known for a long time as an architectural support for the tissues. Many recent data, however, have shown that extracellular matrix macromolecules (collagens, elastin, glycosaminoglycans, proteoglycans and connective tissue glycoproteins) are able to regulate many important cell functions, such as proliferation, migration, protein synthesis or degradation, apoptosis, etc., making them able to play an important role in the wound repair process. Not only the intact macromolecules but some of their specific domains, that we called “Matrikines”, are also able to regulate many cell activities. In this article, we will summarize main findings showing the effects of extracellular matrix macromolecules and matrikines on connective tissue and epithelial cells, particularly in skin, and their potential implication in the wound healing process. These examples show that extracellular matrix macromolecules or some of their specific domains may play a major role in wound healing. Better knowledge of these interactions may suggest new therapeutic targets in wound healing defects. [Copyright &y& Elsevier]
- Published
- 2014
- Full Text
- View/download PDF
36. Endothelial Basement Membrane Components and Their Products, Matrikines: Active Drivers of Pulmonary Hypertension?
- Author
-
Grazyna Kwapiszewska, Katharina Jandl, and Ayse Ceren Mutgan
- Subjects
0301 basic medicine ,Endothelium ,Hypertension, Pulmonary ,endostatin ,vascular remodeling ,Review ,Extracellular matrix ,03 medical and health sciences ,0302 clinical medicine ,laminin ,Laminin ,Medicine ,Humans ,Endothelial dysfunction ,lcsh:QH301-705.5 ,Basement membrane ,Lung ,biology ,IPAH ,business.industry ,Vascular disease ,apoptosis ,type IV collagen ,General Medicine ,medicine.disease ,Pulmonary hypertension ,basement membrane ,Extracellular Matrix ,BMPRII ,matrikines ,030104 developmental biology ,medicine.anatomical_structure ,lcsh:Biology (General) ,030220 oncology & carcinogenesis ,Cancer research ,biology.protein ,business ,barrier function - Abstract
Pulmonary arterial hypertension (PAH) is a vascular disease that is characterized by elevated pulmonary arterial pressure (PAP) due to progressive vascular remodeling. Extracellular matrix (ECM) deposition in pulmonary arteries (PA) is one of the key features of vascular remodeling. Emerging evidence indicates that the basement membrane (BM), a specialized cluster of ECM proteins underlying the endothelium, may be actively involved in the progression of vascular remodeling. The BM and its steady turnover are pivotal for maintaining appropriate vascular functions. However, the pathologically elevated turnover of BM components leads to an increased release of biologically active short fragments, which are called matrikines. Both BM components and their matrikines can interfere with pivotal biological processes, such as survival, proliferation, adhesion, and migration and thus may actively contribute to endothelial dysfunction. Therefore, in this review, we summarize the emerging role of the BM and its matrikines on the vascular endothelium and further discuss its implications on lung vascular remodeling in pulmonary hypertension.
- Published
- 2020
37. Tumor Microenvironment: Extracellular Matrix Alterations Influence Tumor Progression
- Author
-
Monboisse, Jean Claude, Brassart-Pasco, Sylvie, Brézillon, Stéphane, Brassart, Bertrand, Ramont, Laurent, Oudart, Jean-Baptiste, Monboisse, Jean, Matrice extracellulaire et dynamique cellulaire - UMR 7369 (MEDyC), Université de Reims Champagne-Ardenne (URCA)-SFR CAP Santé (Champagne-Ardenne Picardie Santé), and Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Centre National de la Recherche Scientifique (CNRS)
- Subjects
extracellular matrix ,integrins ,cancer ,proteases ,[SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology ,microenvironment ,matrikines - Abstract
International audience; The tumor microenvironment (TME) is composed of various cell types embedded in an altered extracellular matrix (ECM). ECM not only serves as a support for tumor cell but also regulates cell-cell or cell-matrix cross-talks. Alterations in ECM may be induced by hypoxia and acidosis, by oxygen free radicals generated by infiltrating inflammatory cells or by tumor-or stromal cell-secreted proteases. A poorer diagnosis for patients is often associated with ECM alterations. Tumor ECM proteome, also named cancer matrisome, is strongly altered, and different ECM protein signatures may be defined to serve as prognostic biomarkers. Collagen network reorganization facilitates tumor cell invasion. Proteoglycan expression and location are modified in the TME and affect cell invasion and metastatic dissemination. ECM macromolecule degradation by proteases may induce the release of angiogenic growth factors but also the release of proteoglycan-derived or ECM protein fragments, named matrikines or matricryptins. This review will focus on current knowledge and new insights in ECM alterations, degradation, and reticulation through cross-linking enzymes and on the role of ECM fragments in the control of cancer progression and their potential use as biomarkers in cancer diagnosis and prognosis.
- Published
- 2020
38. The Functional Role of Extracellular Matrix Proteins in Cancer.
- Author
-
Popova, Nadezhda V. and Jücker, Manfred
- Subjects
- *
PROTEINS , *DISEASE progression , *EXTRACELLULAR matrix proteins , *COLLAGEN , *FIBRONECTINS , *FIBROBLASTS , *CANCER invasiveness , *CELL physiology , *MATRIX metalloproteinases , *CELL proliferation , *CELL lines - Abstract
Simple Summary: Extracellular matrix is a three-dimensional network of macromolecules that provide structural and biochemical support to surrounding cells. Extracellular matrix plays a critical role in the development and progression of cancer. The extracellular matrix of the tumor is very different from the matrix of the normal tissue. Mainly fibroblasts produce and regulate matrix remodeling, but in cancer, the tumor matrix also originates from cancer cells. We describe the mechanisms of how the protein composition and structure of the extracellular matrix changes during cancer progression and how abnormal matrix deregulates the behavior of stromal cells and influences cancer progression. The extracellular matrix (ECM) is highly dynamic as it is constantly deposited, remodeled and degraded to maintain tissue homeostasis. ECM is a major structural component of the tumor microenvironment, and cancer development and progression require its extensive reorganization. Cancerized ECM is biochemically different in its composition and is stiffer compared to normal ECM. The abnormal ECM affects cancer progression by directly promoting cell proliferation, survival, migration and differentiation. The restructured extracellular matrix and its degradation fragments (matrikines) also modulate the signaling cascades mediated by the interaction with cell-surface receptors, deregulate the stromal cell behavior and lead to emergence of an oncogenic microenvironment. Here, we summarize the current state of understanding how the composition and structure of ECM changes during cancer progression. We also describe the functional role of key proteins, especially tenascin C and fibronectin, and signaling molecules involved in the formation of the tumor microenvironment, as well as the signaling pathways that they activate in cancer cells. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
39. Matrikines and the lungs
- Author
-
Burgess, Janette K. and Weckmann, Markus
- Subjects
- *
LUNG disease treatment , *MOLECULAR structure , *CELLULAR control mechanisms , *EXTRACELLULAR matrix proteins , *EPIDERMAL growth factor , *CLINICAL trials - Abstract
Abstract: The extracellular matrix is a complex network of fibrous and nonfibrous molecules that not only provide structure to the lung but also interact with and regulate the behaviour of the cells which it surrounds. Recently it has been recognised that components of the extracellular matrix proteins are released, often through the action of endogenous proteases, and these fragments are termed matrikines. Matrikines have biological activities, independent of their role within the extracellular matrix structure, which may play important roles in the lung in health and disease pathology. Integrins are the primary cell surface receptors, characterised to date, which are used by the matrikines to exert their effects on cells. However, evidence is emerging for the need for co-factors and other receptors for the matrikines to exert their effects on cells. The potential for matrikines, and peptides derived from these extracellular matrix protein fragments, as therapeutic agents has recently been recognised. The natural role of these matrikines (including inhibitors of angiogenesis and possibly inflammation) make them ideal targets to mimic as therapies. A number of these peptides have been taken forward into clinical trials. The focus of this review will be to summarise our current understanding of the role, and potential for highly relevant actions, of matrikines in lung health and disease. [Copyright &y& Elsevier]
- Published
- 2012
- Full Text
- View/download PDF
40. Matrikines : une nouvelle stratégie thérapeutique anti-cancéreuse.
- Author
-
Monboisse, Jean Claude, Sénéchal, Karine, Thevenard, Jessica, Ramont, Laurent, and Brassart-Pasco, Sylvie
- Subjects
ANTINEOPLASTIC agents ,EXTRACELLULAR matrix ,PEPTIDES ,CANCER invasiveness ,METASTASIS ,HYPOXEMIA ,STROMAL cells - Abstract
The article offers information on the use of matrikines in new anticancer therapeutic strategy. It informs that matrikines are extracellular matrix-derived peptides which regulate cell activity and capable to control tumor invasion and metastasis dissemination. It has been found that during hypoxia proteases secreted by the stromal cells degrade the stromal extracellular matrix which further releases various matrikines.
- Published
- 2012
- Full Text
- View/download PDF
41. An introduction to matrikines: extracellular matrix-derived peptides which regulate cell activity: Implication in tumor invasion
- Author
-
Maquart, François-Xavier, Pasco, Sylvie, Ramont, Laurent, Hornebeck, William, and Monboisse, Jean-Claude
- Subjects
- *
CELLULAR control mechanisms , *ELASTIN , *FIBRONECTINS , *OSTEONECROSIS - Abstract
The term of “matrikines” was coined for designating peptides liberated by partial proteolysis of extracellular matrix macromolecules, which are able to regulate cell activities. Among these peptides, some of them may modulate proliferation, migration, protease production, or apoptosis, which suggest that they can play a significant role in the control of tumor progression. In this introduction, we present the best characterized matrikines, derived from elastin, connective tissue glycoproteins, or collagens. [Copyright &y& Elsevier]
- Published
- 2004
- Full Text
- View/download PDF
42. Tumstatin fragment selectively inhibits neutrophil infiltration in experimental asthma exacerbation
- Author
-
Christina Vock, Markus Weckmann, Lars Lunding, Anna Bachmann, Michael Wegmann, Rainer Bartels, Francesca Tang, Janette K. Burgess, Henrike Hollaender, Tim Becker, Brian G. Oliver, Gyde Nissen, Matthias V. Kopp, Solveig Lemmel, Publica, Groningen Research Institute for Asthma and COPD (GRIAC), and Restoring Organ Function by Means of Regenerative Medicine (REGENERATE)
- Subjects
0301 basic medicine ,Male ,Allergy ,Tumstatin ,Exacerbation ,Neutrophils ,IV COLLAGEN ,Stimulation ,Autoantigens ,ACTIVATION ,Mice ,0302 clinical medicine ,exacerbation ,Immunology and Allergy ,remodelling ,PEPTIDE ,innate immunity ,Middle Aged ,medicine.anatomical_structure ,Neutrophil Infiltration ,030220 oncology & carcinogenesis ,BASEMENT-MEMBRANE ,Disease Progression ,Female ,INFLAMMATORY PHENOTYPES ,medicine.symptom ,NC1 DOMAIN ,Adult ,Collagen Type IV ,medicine.medical_specialty ,Immunology ,Inflammation ,03 medical and health sciences ,Young Adult ,In vivo ,Internal medicine ,medicine ,EXTRACELLULAR-MATRIX ,Animals ,Humans ,Asthma ,Lung ,IDENTIFICATION ,business.industry ,medicine.disease ,In vitro ,Disease Models, Animal ,030104 developmental biology ,Endocrinology ,MATRIKINES ,business ,Peptides ,Reactive Oxygen Species ,ALPHA-3(IV) CHAIN ,Biomarkers - Abstract
Background: Asthma is a chronic inflammatory disease with structural changes present. Burgess and colleagues recently found tumstatin markedly reduced in adult asthmatic lung tissue compared with nonasthmatics. ECM fragments such as tumstatin are named matrikines and act independently of the parent molecule. The role of Col IV matrikines in neutrophil inflammation (eg. exacerbation in asthma) has not been investigated to date. Severe adult asthma phenotypes are dominated by neutrophilic inflammation and show a high frequency of severe exacerbations.Objective: This study sought to investigate the role of a novel active region within tumstatin (CP17) and its implication in neutrophil inflammatory responses related to asthma exacerbation.Methods: For reactive oxygen production, isolated neutrophils were preincubated with peptides or vehicle for 1 hour and stimulated (PMA). Luminescence signal was recorded (integration over 10 seconds) for 1.5 hours. Neutrophil migration was performed according to the SiMA protocol. Mice were sensitized to OVA/Alumn by intraperitoneal (i.p.) injections. Mice were then treated with CP17, vehicle (PBS) or scrambled peptide (SP17) after OVA exposure (days 27 and 28, polyI:C stimulation). All animals were killed on day 29 with lung function measurement, histology and lavage.Results: CP17 decreased total ROS production rate to 52.44% (0.5 mu mol/L, P Conclusion: CP17 reduced the ROS production rate, migrational speed and selectively inhibited neutrophil accumulation in the lung interstitium and lumen.Clinical relevance: CP17 may serve as a potential precursor for drug development to combat overwhelming neutrophil inflammation.
- Published
- 2018
43. Hold on or Cut? Integrin- and MMP-Mediated Cell–Matrix Interactions in the Tumor Microenvironment.
- Author
-
Niland, Stephan and Eble, Johannes A.
- Subjects
- *
TUMOR microenvironment , *MATRIX metalloproteinases , *CELL anatomy , *EXTRACELLULAR matrix , *CANCER invasiveness - Abstract
The tumor microenvironment (TME) has become the focus of interest in cancer research and treatment. It includes the extracellular matrix (ECM) and ECM-modifying enzymes that are secreted by cancer and neighboring cells. The ECM serves both to anchor the tumor cells embedded in it and as a means of communication between the various cellular and non-cellular components of the TME. The cells of the TME modify their surrounding cancer-characteristic ECM. This in turn provides feedback to them via cellular receptors, thereby regulating, together with cytokines and exosomes, differentiation processes as well as tumor progression and spread. Matrix remodeling is accomplished by altering the repertoire of ECM components and by biophysical changes in stiffness and tension caused by ECM-crosslinking and ECM-degrading enzymes, in particular matrix metalloproteinases (MMPs). These can degrade ECM barriers or, by partial proteolysis, release soluble ECM fragments called matrikines, which influence cells inside and outside the TME. This review examines the changes in the ECM of the TME and the interaction between cells and the ECM, with a particular focus on MMPs. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
44. Endothelial Basement Membrane Components and Their Products, Matrikines: Active Drivers of Pulmonary Hypertension?
- Author
-
Mutgan, Ayse Ceren, Jandl, Katharina, and Kwapiszewska, Grazyna
- Subjects
- *
BASAL lamina , *PULMONARY hypertension , *VASCULAR remodeling , *VASCULAR endothelium , *ENDOTHELIUM diseases - Abstract
Pulmonary arterial hypertension (PAH) is a vascular disease that is characterized by elevated pulmonary arterial pressure (PAP) due to progressive vascular remodeling. Extracellular matrix (ECM) deposition in pulmonary arteries (PA) is one of the key features of vascular remodeling. Emerging evidence indicates that the basement membrane (BM), a specialized cluster of ECM proteins underlying the endothelium, may be actively involved in the progression of vascular remodeling. The BM and its steady turnover are pivotal for maintaining appropriate vascular functions. However, the pathologically elevated turnover of BM components leads to an increased release of biologically active short fragments, which are called matrikines. Both BM components and their matrikines can interfere with pivotal biological processes, such as survival, proliferation, adhesion, and migration and thus may actively contribute to endothelial dysfunction. Therefore, in this review, we summarize the emerging role of the BM and its matrikines on the vascular endothelium and further discuss its implications on lung vascular remodeling in pulmonary hypertension. [ABSTRACT FROM AUTHOR]
- Published
- 2020
- Full Text
- View/download PDF
45. Hold on or Cut? Integrin- and MMP-Mediated Cell-Matrix Interactions in the Tumor Microenvironment.
- Author
-
Niland S and Eble JA
- Subjects
- Animals, Extracellular Matrix metabolism, Humans, Matrix Metalloproteinases metabolism, Neoplasms metabolism, Neoplasms pathology, Cell-Matrix Junctions metabolism, Integrins metabolism, Tumor Microenvironment
- Abstract
The tumor microenvironment (TME) has become the focus of interest in cancer research and treatment. It includes the extracellular matrix (ECM) and ECM-modifying enzymes that are secreted by cancer and neighboring cells. The ECM serves both to anchor the tumor cells embedded in it and as a means of communication between the various cellular and non-cellular components of the TME. The cells of the TME modify their surrounding cancer-characteristic ECM. This in turn provides feedback to them via cellular receptors, thereby regulating, together with cytokines and exosomes, differentiation processes as well as tumor progression and spread. Matrix remodeling is accomplished by altering the repertoire of ECM components and by biophysical changes in stiffness and tension caused by ECM-crosslinking and ECM-degrading enzymes, in particular matrix metalloproteinases (MMPs). These can degrade ECM barriers or, by partial proteolysis, release soluble ECM fragments called matrikines, which influence cells inside and outside the TME. This review examines the changes in the ECM of the TME and the interaction between cells and the ECM, with a particular focus on MMPs.
- Published
- 2020
- Full Text
- View/download PDF
46. Mesenchymal Stem Cells from Adipose Tissue in Clinical Applications for Dermatological Indications and Skin Aging
- Author
-
Victoria V. Lunyak, Marek Dobke, and Meenakshi Gaur
- Subjects
0301 basic medicine ,Pathology ,medicine.medical_specialty ,Adipose tissue ,wound healing ,Review ,Mesenchymal Stem Cell Transplantation ,clinical applications ,Bioinformatics ,Epidermal homeostasis ,Skin Diseases ,Catalysis ,Skin Aging ,lcsh:Chemistry ,Inorganic Chemistry ,03 medical and health sciences ,Immune system ,epidermis ,medicine ,Animals ,Humans ,Regeneration ,Rejuvenation ,Physical and Theoretical Chemistry ,lcsh:QH301-705.5 ,Molecular Biology ,Spectroscopy ,Tissue homeostasis ,subcutaneous adipose depot ,business.industry ,aging ,Organic Chemistry ,Mesenchymal stem cell ,Mesenchymal Stem Cells ,General Medicine ,dermis ,matrikines ,Computer Science Applications ,030104 developmental biology ,Adipose Tissue ,lcsh:Biology (General) ,lcsh:QD1-999 ,skin homeostasis ,adipose-derived stem cells ,Stem cell ,business ,Wound healing - Abstract
Operating at multiple levels of control, mesenchymal stem cells from adipose tissue (ADSCs) communicate with organ systems to adjust immune response, provide signals for differentiation, migration, enzymatic reactions, and to equilibrate the regenerative demands of balanced tissue homeostasis. The identification of the mechanisms by which ADSCs accomplish these functions for dermatological rejuvenation and wound healing has great potential to identify novel targets for the treatment of disorders and combat aging. Herein, we review new insights into the role of adipose-derived stem cells in the maintenance of dermal and epidermal homeostasis, and recent advances in clinical applications of ADSCs related to dermatology.
- Published
- 2017
47. Stabilized Collagen and Elastin-Based Scaffolds for Mitral Valve Tissue Engineering.
- Author
-
Deborde C, Simionescu DT, Wright C, Liao J, Sierad LN, and Simionescu A
- Subjects
- Adipose Tissue cytology, Adipose Tissue metabolism, Animals, Extracellular Matrix chemistry, Humans, Hydrolyzable Tannins, Stem Cells cytology, Stem Cells metabolism, Swine, Tissue Engineering, Bioprosthesis, Collagen chemistry, Elastin chemistry, Heart Valve Prosthesis, Mitral Valve, Tissue Scaffolds chemistry
- Abstract
There is a significant clinical need for new approaches to treatment of mitral valve disease. The aim of this study was to develop a tissue-engineered mitral valve scaffold possessing appropriate composition and structure to ensure ideal characteristics of mitral valves, such as large orifice, rapid opening and closure, maintenance of mitral annulus-papillary muscle continuity, in vivo biocompatibility and extended durability. An extracellular matrix-based scaffold was generated, based on the native porcine mitral valve as starting material and a technique for porcine cell removal without causing damage to the matrix components. To stabilize these structures and slow down their degradation, acellular scaffolds were treated with penta-galloyl glucose (PGG), a well-characterized polyphenol with high affinity for collagen and elastin. Biaxial mechanical testing presented similar characteristics for the PGG-treated scaffolds compared to fresh tissues. The extracellular matrix components, crucial for maintaining the valve shape and function, were well preserved in leaflets, and in chordae, as shown by their resistance to collagenase and elastin. When extracted with strong detergents, the PGG-treated scaffolds released a reduced amount of soluble matrix peptides, compared to untreated scaffolds; this correlated with diminished activation of fibroblasts seeded on scaffolds treated with PGG. Cell-seeded scaffolds conditioned for 5 weeks in a valve bioreactor showed good cell viability. Finally, rat subdermal implantation studies showed that PGG-treated mitral valve scaffolds were biocompatible, nonimmunogenic, noninflammatory, and noncalcifying. In conclusion, a biocompatible mitral valve scaffold was developed, which preserved the biochemical composition and structural integrity of the valve, essential for its highly dynamic mechanical demands, and its biologic durability., Competing Interests: Statement No competing financial interests exist.
- Published
- 2016
- Full Text
- View/download PDF
48. Identification of Small Peptides of Acidic Collagen Extracts from Silver Carp Skin and Their Therapeutic Relevance.
- Author
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Wojtkowiak D, Frydrychowski AF, Hadzik J, and Dominiak M
- Subjects
- Animals, Chromatography, High Pressure Liquid, Collagen chemistry, Decorin isolation & purification, Fish Proteins chemistry, Fish Proteins pharmacology, Histones isolation & purification, Hydrogen-Ion Concentration, Lumican isolation & purification, Protein Conformation, alpha-Helical, Protein Denaturation, Proteomics methods, Spectrophotometry, Ultraviolet, Structure-Activity Relationship, Tandem Mass Spectrometry, Temperature, Carps metabolism, Collagen isolation & purification, Fish Proteins isolation & purification, Skin chemistry
- Abstract
Background: Low-temperature techniques that prevent protein denaturation are being used to extract collagen from fish skin for cosmetic purposes. These extracts contain collagen with its triple helix structure preserved, as well as a number of other proteins., Objectives: The aim of the study was to investigate collagen extracts from the skin of silver carp for the presence of small-molecule peptides., Material and Methods: Liquid chromatography-mass spectrometry (HPLC-MS) was performed to analyze collagen extracts from silver carp skin for the presence of small-molecule peptides., Results: A large number of different peptides were detected in the silver carp skin collagen extracts analyzed. Among the smaller peptides, the most abundant were those of 7-29 aminoacids originating from the following proteins: collagen Iα1, collagen Iα2, collagen Iα3, collagen VIα3, decorin, lumican, histone H2A, histone H2B and histone H4., Conclusions: The study demonstrated that, in addition to high-molecular-weight collagen proteins, acidic collagen extracts acquired from the skin of silver carp at temperatures up to 16°C also contain considerable amounts of small 7-29 amino-acid peptides. The application of these peptides could therefore be expected to result in beneficial clinical effects in patients in need of reconstructive treatment.
- Published
- 2016
- Full Text
- View/download PDF
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