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5. MOESM1 of In vitro effects of interleukin (IL)-1 beta inhibition on the epithelial-to-mesenchymal transition (EMT) of renal tubular and hepatic stellate cells

Author

Masola, Valentina, Carraro, Amedeo, Granata, Simona, Signorini, Lorenzo, Bellin, Gloria, Violi, Paola, Lupo, Antonio, Tedeschi, Umberto, Onisto, Maurizio, Gambaro, Giovanni, and Zaza, Gianluigi

Abstract

Additional file 1: Figure S1. Gene expression of Metalloproteinase-9 (Mmp-9) in HK-2. Figure S2. Enzymatic activity of MMP-9 in HK-2. Figure S3. Gene expression of Metalloproteinase-9 (Mmp-9) in LX-2. Figure S4. Enzymatic activity of MMP-9 in LX-2.

Published
2019
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9. Metal Nanoparticles Released from Dental Implant Surfaces: Potential Contribution to Chronic Inflammation and Peri-Implant Bone Loss

Author

Bressan, Eriberto, primary, Ferroni, Letizia, additional, Gardin, Chiara, additional, Bellin, Gloria, additional, Sbricoli, Luca, additional, Sivolella, Stefano, additional, Brunello, Giulia, additional, Schwartz-Arad, Devorah, additional, Mijiritsky, Eitan, additional, Penarrocha, Miguel, additional, Penarrocha, David, additional, Taccioli, Cristian, additional, Tatullo, Marco, additional, Piattelli, Adriano, additional, and Zavan, Barbara, additional

Published
2019
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18. Heparanase regulates the M1 polarization of renal macrophages and their crosstalk with renal epithelial tubular cells after ischemia/reperfusion injury

Author

Masola, Valentina, Zaza, Gianluigi, Bellin, Gloria, Dall'Olmo, Luigi, Granata, Simona, Vischini, Gisella, Secchi, Maria Francesca, Lupo, Antonio, Gambaro, Giovanni, Onisto, Maurizio, Gambaro, Giovanni (ORCID:0000-0001-5733-2370), Masola, Valentina, Zaza, Gianluigi, Bellin, Gloria, Dall'Olmo, Luigi, Granata, Simona, Vischini, Gisella, Secchi, Maria Francesca, Lupo, Antonio, Gambaro, Giovanni, Onisto, Maurizio, and Gambaro, Giovanni (ORCID:0000-0001-5733-2370)

Abstract

Heparanase (HPSE) is part of the biologic network triggered by ischemia/reperfusion (I/R) injury, a complication of renal transplantation and acute kidney injury. During this period, the kidney or graft undergoes a process ofmacrophages recruitment andactivation.HPSE may therefore control these biologic effects. We measured the ability of HPSE and its inhibitor, SST0001, to regulate macrophage polarization and the crosstalk between macrophages and HK-2 renal tubular cells during in vitro hypoxia/reoxygenation (H/R). Furthermore, we evaluated in vivo renal inflammation, macrophage polarization, and histologic changes in mice subjected to monolateral I/R and treated with SST0001 for 2 or 7 d. The in vitro experiments showed that HPSE sustained M1 macrophage polarization and modulated apoptosis, the release of damage associated molecular patterns in post-H/R tubular cells, the synthesis of proinflammatory cytokines, and the up-regulation of TLRs on both epithelial cells and macrophages. HPSE also regulated M1 polarization induced by H/R-injured tubular cells and the partial epithelial-mesenchymal transition of these epithelial cells byM1macrophages.All these effectswere prevented by inhibiting HPSE. Furthermore, the inhibition of HPSE in vivo reduced inflammation andM1 polarization in mice undergoing I/R injury, partially restored renal function and normal histology, and reduced apoptosis. These results show for the first time that HPSE regulates macrophage polarization as well as renal damage and repair after I/R. HPSE inhibitors could therefore provide a new pharmacologic approach to minimize acute kidney injury and to prevent the chronic profibrotic damages inducedby I/R.-Masola,V.,Zaza,G.,Bellin,G.,Dall'Olmo,L.,Granata,S., Vischini, G., Secchi, M. F., Lupo, A., Gambaro, G., Onisto, M. Heparanase regulates the M1 polarization of renal macrophages and their crosstalk with renal epithelial tubular cells after ischemia/reperfusion injury. FASEB J. 32, 742-756 (2018). w

Published
2018

19. Heparanase regulates the M1 polarization of renal macrophages and their crosstalk with renal epithelial tubular cells after ischemia/reperfusion injury

Author

Masola, Valentina, primary, Zaza, Gianluigi, additional, Bellin, Gloria, additional, Dall'Olmo, Luigi, additional, Granata, Simona, additional, Vischini, Gisella, additional, Francesca Secchi, Maria, additional, Lupo, Antonio, additional, Gambaro, Giovanni, additional, and Onisto, Maurizio, additional

Published
2018
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20. Transcriptomics: A Step behind the Comprehension of the Polygenic Influence on Oxidative Stress, Immune Deregulation, and Mitochondrial Dysfunction in Chronic Kidney Disease

Author

Granata, Simona, Dalla Gassa, Alessandra, Bellin, Gloria, Lupo, Antonio, and Zaza, Gianluigi

Subjects
Article Subject
Abstract

Chronic kidney disease (CKD) is an increasing and global health problem with a great economic burden for healthcare system. Therefore to slow down the progression of this condition is a main objective in nephrology. It has been extensively reported that microinflammation, immune system deregulation, and oxidative stress contribute to CKD progression. Additionally, dialysis worsens this clinical condition because of the contact of blood with bioincompatible dialytic devices. Numerous studies have shown the close link between immune system impairment and CKD but most have been performed using classical biomolecular strategies. These methodologies are limited in their ability to discover new elements and enable measuring the simultaneous influence of multiple factors. The “omics” techniques could overcome these gaps. For example, transcriptomics has revealed that mitochondria and inflammasome have a role in pathogenesis of CKD and are pivotal elements in the cellular alterations leading to systemic complications. We believe that a larger employment of this technique, together with other “omics” methodologies, could help clinicians to obtain new pathogenetic insights, novel diagnostic biomarkers, and therapeutic targets. Finally, transcriptomics could allow clinicians to personalize therapeutic strategies according to individual genetic background (nutrigenomic and pharmacogenomic). In this review, we analyzed the available transcriptomic studies involving CKD patients.

Published
2016
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22. Involvement of heparanase in the pathogenesis of acute kidney injury: nephroprotective effect of PG545

Author

Abassi, Zaid, primary, Hamoud, Shadi, additional, Hassan, Ahmad, additional, Khamaysi, Iyad, additional, Nativ, Omri, additional, Heyman, Samuel N., additional, Muhammad, Rabia Shekh, additional, Ilan, Neta, additional, Singh, Preeti, additional, Hammond, Edward, additional, Zaza, Gianluigi, additional, Lupo, Antonio, additional, Onisto, Maurizio, additional, Bellin, Gloria, additional, Masola, Valentina, additional, Vlodavsky, Israel, additional, and Gambaro, Giovani, additional

Published
2017
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24. Heparanase: A Potential New Factor Involved in the Renal Epithelial Mesenchymal Transition (EMT) Induced by Ischemia/Reperfusion (I/R) Injury

Author

Masola, Valentina, primary, Zaza, Gianluigi, additional, Gambaro, Giovanni, additional, Onisto, Maurizio, additional, Bellin, Gloria, additional, Vischini, Gisella, additional, Khamaysi, Iyad, additional, Hassan, Ahmad, additional, Hamoud, Shadi, additional, Nativ, Omri, additional, N. Heyman, Samuel, additional, Lupo, Antonio, additional, Vlodavsky, Israel, additional, and Abassi, Zaid, additional

Published
2016
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25. MP079HEPARANASE: A POTENTIAL NEW FACTOR INVOLVED IN THE PRO-FIBROTIC RENAL BIOLOGICAL MACHINERY ACTIVATED BY THE ISCHEMIA-REPERFUSION INJURY

Author

Masola, Valentina, primary, Zaza, Gianluigi, additional, Gambaro, Giovanni, additional, Onisto, Maurizio, additional, Bellin, Gloria, additional, Vischini, Gisella, additional, Khamaysi, Iyad, additional, Hassan, Ahmad, additional, Hamoud, Shadi, additional, Nativ, Omri, additional, Heyman, Samuel N., additional, Lupo, Antonio, additional, Vlodavsky, Israel, additional, and Abassi, Zaid, additional

Published
2016
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26. MP094EVEROLIMUS-INDUCED EPITHELIAL TO MESENCHYMAL TRANSITION IN BRONCHIAL AND PULMONARY CELLS: WHEN THE DOSAGE DOES MATTER IN TRANSPLANTATION

Author

Tomei, Paola, primary, Masola, Valentina, additional, Carratù, Pierluigi, additional, Ventura, Valentina Anna, additional, Granata, Simona, additional, Dalla Gassa, Alessandra, additional, Bellin, Gloria, additional, Onisto, Maurizio, additional, Resta, Onofrio, additional, Gambaro, Giovanni, additional, Lupo, Antonio, additional, and Zaza, Gianluigi, additional

Published
2016
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30. Collagen Fiber Array of Peritumoral Stroma Influences Epithelial-to-Mesenchymal Transition and Invasive Potential of Mammary Cancer Cells

Author

Marco Franchi, Zoi Piperigkou, Konstantinos Athanasios Karamanos, Valentina Masola, Maurizio Onisto, Gloria Bellin, Franchi, Marco, Masola, Valentina, Bellin, Gloria, Onisto, Maurizio, Karamanos, Konstantinos-Athanasio, and Piperigkou, Zoi

Subjects
extracellular matrix, collagen type I, lcsh:Medicine, Matrix (biology), Fibril, Article, Metastasis, Extracellular matrix, 03 medical and health sciences, 0302 clinical medicine, breast cancer, medicine, Epithelial–mesenchymal transition, 030304 developmental biology, Basement membrane, 0303 health sciences, business.industry, lcsh:R, scanning electron microscope, epithelial-to-mesenchymal transition, General Medicine, medicine.disease, Microvesicles, Cell biology, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Cancer cell, business
Abstract

Interactions of cancer cells with matrix macromolecules of the surrounding tumor stroma are critical to mediate invasion and metastasis. In this study, we reproduced the collagen mechanical barriers in vitro (i.e., basement membrane, lamina propria under basement membrane, and deeper bundled collagen fibers with different array). These were used in 3D cell cultures to define their effects on morphology and behavior of breast cancer cells with different metastatic potential (MCF-7 and MDA-MB-231) using scanning electron microscope (SEM). We demonstrated that breast cancer cells cultured in 2D and 3D cultures on different collagen substrates show different morphologies: i) a globular/spherical shape, ii) a flattened polygonal shape, and iii) elongated/fusiform and spindle-like shapes. The distribution of different cell shapes changed with the distinct collagen fiber/fibril physical array and size. Dense collagen fibers, parallel to the culture plane, do not allow the invasion of MCF-7 and MDA-MB-231 cells, which, however, show increases of microvilli and microvesicles, respectively. These novel data highlight the regulatory role of different fibrillar collagen arrays in modifying breast cancer cell shape, inducing epithelial-to-mesenchymal transition, changing matrix composition and modulating the production of extracellular vesicles. Further investigation utilizing this in vitro model will help to demonstrate the biological roles of matrix macromolecules in cancer cell invasion in vivo.

Published
2019

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