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1. Influence of AAV vector tropism on long-term expression and Fc-γ receptor binding of an antibody targeting SARS-CoV-2

Author

Wagner, Jannik T., Müller-Schmucker, Sandra M., Wang, Wenjun, Arnold, Philipp, Uhlig, Nadja, Issmail, Leila, Eberlein, Valentina, Damm, Dominik, Roshanbinfar, Kaveh, Ensser, Armin, Oltmanns, Friederike, Peter, Antonia Sophia, Temchura, Vladimir, Schrödel, Silke, Engel, Felix B., Thirion, Christian, Grunwald, Thomas, Wuhrer, Manfred, Grimm, Dirk, and Überla, Klaus

Published
2024
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3. Large-scale microRNA functional high-throughput screening identifies miR-515-3p and miR-519e-3p as inducers of human cardiomyocyte proliferation

Author

Renikunta, Harsha V., Lazarow, Katina, Gong, Yiqi, Shukla, Praphulla Chandra, Nageswaran, Vanasa, Giral, Hector, Kratzer, Adelheid, Opitz, Lennart, Engel, Felix B., Haghikia, Arash, Costantino, Sarah, Paneni, Francesco, von Kries, Jens Peter, Streckfuss-Bömeke, Katrin, Landmesser, Ulf, and Jakob, Philipp

Published
2023
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4. The EMT transcription factor ZEB1 governs a fitness-promoting but vulnerable DNA replication stress response

Author

Schuhwerk, Harald, Kleemann, Julia, Gupta, Pooja, van Roey, Ruthger, Armstark, Isabell, Kreileder, Martina, Feldker, Nora, Ramesh, Vignesh, Hajjaj, Yussuf, Fuchs, Kathrin, Mahapatro, Mousumi, Hribersek, Mojca, Volante, Marco, Groenewoud, Arwin, Engel, Felix B., Ceppi, Paolo, Eckstein, Markus, Hartmann, Arndt, Müller, Fabian, Kroll, Torsten, Stemmler, Marc P., Brabletz, Simone, and Brabletz, Thomas

Published
2022
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9. Adhesion G Protein-Coupled Receptor Gpr126 (Adgrg6) Expression Profiling in Diseased Mouse, Rat, and Human Kidneys.

Author

Kösters, Peter, Cazorla-Vázquez, Salvador, Krüger, René, Daniel, Christoph, Vonbrunn, Eva, Amann, Kerstin, and Engel, Felix B.

Subjects
G protein coupled receptors, FOCAL segmental glomerulosclerosis, PARIETAL cells, KIDNEYS, ACUTE kidney failure
Abstract

Uncovering the function of understudied G protein-coupled receptors (GPCRs) provides a wealth of untapped therapeutic potential. The poorly understood adhesion GPCR Gpr126 (Adgrg6) is widely expressed in developing kidneys. In adulthood, Gpr126 expression is enriched in parietal epithelial cells (PECs) and epithelial cells of the collecting duct and urothelium. Whether Gpr126 plays a role in kidney disease remains unclear. Here, we characterized Gpr126 expression in diseased kidneys in mice, rats, and humans. RT-PCR data show that Gpr126 expression is altered in kidney disease. A quantitative RNAscope® analysis utilizing cell type-specific markers revealed that Gpr126 expression upon tubular damage is mainly increased in cell types expressing Gpr126 under healthy conditions as well as in cells of the distal and proximal tubules. Upon glomerular damage, an increase was mainly detected in PECs. Notably, Gpr126 expression was upregulated in an ischemia/reperfusion model within hours, while upregulation in a glomerular damage model was only detected after weeks. An analysis of kidney microarray data from patients with lupus nephritis, IgA nephropathy, focal segmental glomerulosclerosis (FSGS), hypertension, and diabetes as well as single-cell RNA-seq data from kidneys of patients with acute kidney injury and chronic kidney disease indicates that GPR126 expression is also altered in human kidney disease. In patients with FSGS, an RNAscope® analysis showed that GPR126 mRNA is upregulated in PECs belonging to FSGS lesions and proximal tubules. Collectively, we provide detailed insights into Gpr126 expression in kidney disease, indicating that GPR126 is a potential therapeutic target. [ABSTRACT FROM AUTHOR]

Published
2024
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13. Non-professional phagocytosis: a general feature of normal tissue cells

Author

Seeberg, Jacob C., Loibl, Monika, Moser, Fabian, Schwegler, Manuela, Büttner-Herold, Maike, Daniel, Christoph, Engel, Felix B., Hartmann, Arndt, Schlötzer-Schrehardt, Ursula, Goppelt-Struebe, Margarete, Schellerer, Vera, Naschberger, Elisabeth, Ganzleben, Ingo, Heinzerling, Lucie, Fietkau, Rainer, and Distel, Luitpold V.

Published
2019
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18. Adhesion GPCR Gpr126 (Adgrg6) Expression Profiling in Zebrafish, Mouse, and Human Kidney.

Author

Cazorla-Vázquez, Salvador, Kösters, Peter, Bertz, Simone, Pfister, Frederick, Daniel, Christoph, Dedden, Mark, Zundler, Sebastian, Jobst-Schwan, Tilman, Amann, Kerstin, and Engel, Felix B.

Subjects
BRACHYDANIO, MICE, KIDNEY development, G protein coupled receptors, PARIETAL cells, KIDNEYS, KIDNEY physiology, EPITHELIAL cells
Abstract

Adhesion G protein-coupled receptors (aGPCRs) comprise the second-largest class of GPCRs, the most common target for approved pharmacological therapies. aGPCRs play an important role in development and disease and have recently been associated with the kidney. Several aGPCRs are expressed in the kidney and some aGPCRs are either required for kidney development or their expression level is altered in diseased kidneys. Yet, general aGPCR function and their physiological role in the kidney are poorly understood. Here, we characterize in detail Gpr126 (Adgrg6) expression based on RNAscope® technology in zebrafish, mice, and humans during kidney development in adults. Gpr126 expression is enriched in the epithelial linage during nephrogenesis and persists in the adult kidney in parietal epithelial cells, collecting ducts, and urothelium. Single-cell RNAseq analysis shows that gpr126 expression is detected in zebrafish in a distinct ionocyte sub-population. It is co-detected selectively with slc9a3.2, slc4a4a, and trpv6, known to be involved in apical acid secretion, buffering blood or intracellular pH, and to maintain high cytoplasmic Ca2+ concentration, respectively. Furthermore, gpr126-expressing cells were enriched in the expression of potassium transporter kcnj1a.1 and gcm2, which regulate the expression of a calcium sensor receptor. Notably, the expression patterns of Trpv6, Kcnj1a.1, and Gpr126 in mouse kidneys are highly similar. Collectively, our approach permits a detailed insight into the spatio-temporal expression of Gpr126 and provides a basis to elucidate a possible role of Gpr126 in kidney physiology. [ABSTRACT FROM AUTHOR]

Published
2023
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19. EGFL7 ligates αvβ3 integrin to enhance vessel formation

Author

Nikolić, Iva, Stanković, Nevenka Dudvarski, Bicker, Frank, Meister, Jeannette, Braun, Helene, Awwad, Khader, Baumgart, Jan, Simon, Kirsten, Thal, Serge C., Patra, Chinmoy, Harter, Patrick N., Plate, Karl H., Engel, Felix B., Dimmeler, Stefanie, Eble, Johannes A., Mittelbronn, Michel, Schäfer, Michael K., Jungblut, Benno, Chavakis, Emmanouil, Fleming, Ingrid, and Schmidt, Mirko H.H.

Published
2013
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21. Melatonin as a cardioprotective therapy following ST-segment elevation myocardial infarction: is it really promising? Reply

Author

Hausenloy, Derek J., Garcia-Dorado, David, Erik Bøtker, Hans, Davidson, Sean M., Downey, James, Engel, Felix B., Jennings, Robert, Lecour, Sandrine, Leor, Jonathan, Madonna, Rosalinda, Ovize, Michel, Perrino, Cinzia, Prunier, Fabrice, Schulz, Rainer, Sluijter, Joost P. G., Van Laake, Linda W., Vinten-Johansen, Jakob, Yellon, Derek M., Ytrehus, Kirsti, Heusch, Gerd, and Ferdinandy, Péter

Published
2017
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22. Novel targets and future strategies for acute cardioprotection: Position Paper of the European Society of Cardiology Working Group on Cellular Biology of the Heart

Author

Hausenloy, Derek J., Garcia-Dorado, David, Bøtker, Hans Erik, Davidson, Sean M., Downey, James, Engel, Felix B., Jennings, Robert, Lecour, Sandrine, Leor, Jonathan, Madonna, Rosalinda, Ovize, Michel, Perrino, Cinzia, Prunier, Fabrice, Schulz, Rainer, Sluijter, Joost P.G., Van Laake, Linda W., Vinten-Johansen, Jakob, Yellon, Derek M., Ytrehus, Kirsti, Heusch, Gerd, and Ferdinandy, Péter

Published
2017
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28. Position Paper of the European Society of Cardiology Working Group Cellular Biology of the Heart: cell-based therapies for myocardial repair and regeneration in ischemic heart disease and heart failure

Author

Madonna, Rosalinda, Van Laake, Linda W., Davidson, Sean M., Engel, Felix B., Hausenloy, Derek J., Lecour, Sandrine, Leor, Jonathan, Perrino, Cinzia, Schulz, Rainer, Ytrehus, Kirsti, Landmesser, Ulf, Mummery, Christine L., Janssens, Stefan, Willerson, James, Eschenhagen, Thomas, Ferdinandy, Péter, and Sluijter, Joost P.G.

Published
2016
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29. GSK3ß-dependent dysregulation of neurodevelopment in SPG11-patient induced pluripotent stem cell model

Author

Mishra, Himanshu K., Prots, Iryna, Havlicek, Steven, Kohl, Zacharias, Perez-Branguli, Francesc, Boerstler, Tom, Anneser, Lukas, Minakaki, Georgia, Wend, Holger, Hampl, Martin, Leone, Marina, Brückner, Martina, Klucken, Jochen, Reis, Andre, Boyer, Leah, Schuierer, Gerhard, Behrens, Jürgen, Lampert, Angelika, Engel, Felix B., Gage, Fred H., Winkler, Jürgen, and Winner, Beate

Published
2016
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30. Structural and Geochemical Assessment of the Coralline Alga Tethysphytum antarcticum from Terra Nova Bay, Ross Sea, Antarctica.

Author

López Correa, Matthias, Teichert, Sebastian, Ragazzola, Federica, Cazorla Vázquez, Salvador, Engel, Felix B., Hurle, Katrin, Mazzoli, Claudio, Kuklinski, Piotr, Raiteri, Giancarlo, and Lombardi, Chiara

Subjects
CORALLINE algae, BASE pairs, GENITALIA, LOW temperatures, MOLECULAR genetics
Abstract

Crustose coralline algae (CCA) occur from the tropics to the poles in photic benthic environments. Here, we report on some of the world's southernmost and coldest CCA sites in Terra Nova, Ross Sea, Antarctica at 74°41′ S. The recently described red alga Tethysphytum antarticum is investigated for its skeletal architecture, its mineralogical and geochemical composition, as well as for its taxonomic classification. A phylogenetic analysis based on molecular genetics and the sequencing of the photosystem II protein D1 (psbA) gave a perfect match with T. antarcticum. Histological sections and micro-CT-scans provide new diagnostic details for the conceptacles (the reproductive organs of the alga). X-ray diffractometry and electron-microprobe measurements yielded a clear high-Mg calcite (~8 mol%) composition of the skeletal parts. Detailed back-scattered electron imaging of polished petrographic thin sections revealed a two-layered thallus (vegetative plant tissue), comprising an organic-rich irregularly calcified basal layer with rectangular cells, overlain by the main thallus. Elemental maps show relatively increased sulphur in the basal layer, clearly tied to organic cell walls. MgCO3 and SrCO3 were targeted with semiquantitative elemental mappings and in an ontogenetic quantitative spot transect. Compared with temperature (−1.95 °C to +1.08 °C), the MgCO3 (mol%) reflects this world's coldest CCA site temperature with the lowest MgCO3 content of 7.9 ± 1.6 mol%. The along transect variability, however, shows with ~6 mol% a larger MgCO3 variability than expected for the 3 °C intra-annual temperature amplitude in Terra Nova Bay. This implies that in low amplitude settings the biomineralisation control on Mg/Ca ratios can outcompete its temperature sensitivity. Mark-recapture studies, next to the environmental logger station La Zecca are suggested, to perform a detailed growth rate and biomineralisation quantification. [ABSTRACT FROM AUTHOR]

Published
2023
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31. From basic mechanisms to clinical applications in heart protection, new players in cardiovascular diseases and cardiac theranostics: meeting report from the third international symposium on “New frontiers in cardiovascular research”

Author

Cabrera-Fuentes, Hector A., Aragones, Julian, Bernhagen, Jürgen, Boening, Andreas, Boisvert, William A., Bøtker, Hans E., Bulluck, Heerajnarain, Cook, Stuart, Di Lisa, Fabio, Engel, Felix B., Engelmann, Bernd, Ferrazzi, Fulvia, Ferdinandy, Péter, Fong, Alan, Fleming, Ingrid, Gnaiger, Erich, Hernández-Reséndiz, Sauri, Kalkhoran, Siavash Beikoghli, Kim, Moo Hyun, Lecour, Sandrine, Liehn, Elisa A., Marber, Michael S., Mayr, Manuel, Miura, Tetsuji, Ong, Sang-Bing, Peter, Karlheinz, Sedding, Daniel, Singh, Manvendra K., Suleiman, M. Saadeh, Schnittler, Hans J., Schulz, Rainer, Shim, Winston, Tello, Daniel, Vogel, Carl-Wilhelm, Walker, Malcolm, Li, Qilong Oscar Yang, Yellon, Derek M., Hausenloy, Derek J., and Preissner, Klaus T.

Published
2016
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34. New functions and signaling mechanisms for the class of adhesion G protein–coupled receptors

Author

Liebscher, Ines, Ackley, Brian, Araç, Demet, Ariestanti, Donna M., Aust, Gabriela, Bae, Byoung-il, Bista, Bigyan R., Bridges, James P., Duman, Joseph G., Engel, Felix B., Giera, Stefanie, Goffinet, André M., Hall, Randy A., Hamann, Jörg, Hartmann, Nicole, Lin, Hsi-Hsien, Liu, Mingyao, Luo, Rong, Mogha, Amit, Monk, Kelly R., Peeters, Miriam C., Prömel, Simone, Ressl, Susanne, Schiöth, Helgi B., Sigoillot, Séverine M., Song, Helen, Talbot, William S., Tall, Gregory G., White, James P., Wolfrum, Uwe, Xu, Lei, and Piao, Xianhua

Published
2014
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35. Novel therapeutic strategies for cardioprotection

Author

Sluijter, Joost P.G., Condorelli, Gianluigi, Davidson, Sean M., Engel, Felix B., Ferdinandy, Peter, Hausenloy, Derek J., Lecour, Sandrine, Madonna, Rosalinda, Ovize, Michel, Ruiz-Meana, Marisol, Schulz, Rainer, and Van Laake, Linda W.

Published
2014
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36. Hypoxia-inducible factor induces local thyroid hormone inactivation during hypoxic-ischemic disease in rats

Author

Simonides, Warner S., Mulcahey, Michelle A., Redout, Everaldo M., Muller, Alice, Zuidwijk, Marian J., Visser, Theo J., Wassen, Frank W.J.S., Crescenzi, Alessandra, da-Silva, Wagner S., Harney, John, Engel, Felix B., Obregon, Maria-Jesus, Larsen P. Reed, Bianco, Antonio C., and Huang, Stephen A.

Subjects
Critically ill -- Health aspects, Critically ill -- Medical examination, Critically ill -- Research, Thyroid hormones -- Health aspects, Thyroid hormones -- Physiological aspects, Thyroid hormones -- Research, Hypoxia -- Risk factors, Hypoxia -- Genetic aspects, Hypoxia -- Care and treatment, Hypoxia -- Research
Abstract

Thyroid hormone is a critical determinant of cellular metabolism and differentiation. Precise tissue-specific regulation of the active ligand 3,5,3'-triiodothyronine (T3) is achieved by the sequential removal of iodine groups from the thyroid hormone molecule, with type 3 deiodinase (D3) comprising the major inactivating pathway that terminates the action of T3 and prevents activation of the prohormone thyroxine. Using cells endogenously expressing D3, we found that hypoxia induced expression of the D3 gene DIO3 by a hypoxia-inducible factor--dependent (HIF-dependent) pathway. D3 activity and mRNA were increased both by hypoxia and by hypoxia mimetics that increase HIF-1. Using ChIP, we found that HIF-1[alpha] interacted specifically with the DIO3 promoter, indicating that DIO3 may be a direct transcriptional target of HIF-1. Endogenous D3 activity decreased T3-dependent oxygen consumption in both neuronal and hepatocyte cell lines, suggesting that hypoxia-induced D3 may reduce metabolic rate in hypoxic tissues. Using a rat model of cardiac failure due to RV hypertrophy, we found that HIF-1[alpha] and D3 proteins were induced specifically in the hypertrophic myocardium of the RV, creating an anatomically specific reduction in local T3 content and action. These results suggest a mechanism of metabolic regulation during hypoxic-ischemic injury in which HIF-1 reduces local thyroid hormone signaling through induction of D3., Introduction During illness, humans experience a fall in serum thyroid hormones termed the nonthyroidal illness syndrome (1). An inverse relationship between serum thyroxine (T4) and mortality in critically ill patients [...]

Published
2008

37. p38 MAP kinase inhibition enables proliferation of adult mammalian cardiomyocytes

Author

Engel, Felix B., Schebesta, Michael, Duong, Mychelle T., Gang Lu, Ren, Shuxun, Madwed, Jeffery B., Huiping Jiang, Yibin Wang, and Keating, Mark T.

Subjects
Cell proliferation -- Research, Protein kinases -- Research, Heart cells -- Research, Genetic research, Biological sciences
Abstract

A study shows that the adult mammalian cardiomyocytes cells can divide and the p38 MAP kinase activity is the important mechanism used by mammalian cardiomyocytes to control cell cycle. The findings of the study establish that p38 is the key negative regulator of cardiomyocyte proliferation indicating that adult cardiomyocytes can divide.

Published
2005

40. Dissecting signaling and functions of adhesion G protein–coupled receptors

Author

Araç, Demet, Aust, Gabriela, Calebiro, Davide, Engel, Felix B., Formstone, Caroline, Goffinet, André, Hamann, Jörg, Kittel, Robert J., Liebscher, Ines, Lin, Hsi-Hsien, Monk, Kelly R., Petrenko, Alexander, Piao, Xianhua, Prömel, Simone, Schiöth, Helgi B., Schwartz, Thue W., Stacey, Martin, Ushkaryov, Yuri A., Wobus, Manja, Wolfrum, Uwe, Xu, Lei, and Langenhan, Tobias

Published
2012
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45. ESC Working Group on Cellular Biology of the Heart: position paper for Cardiovascular Research: tissue engineering strategies combined with cell therapies for cardiac repair in ischaemic heart disease and heart failure : Position paper for Cardiovascular Research: Tissue engineering strategies combined with cell therapies for cardiac repair in ischaemic heart disease and heart failure

Author

Madonna, Rosalinda, Van Laake, Linda W, Botker, Hans Erik, Davidson, Sean M, De Caterina, Raffaele, Engel, Felix B, Eschenhagen, Thomas, Fernandez-Aviles, Francesco, Hausenloy, Derek J, Hulot, Jean-Sebastien, Lecour, Sandrine, Leor, Jonathan, Menasché, Philippe, Pesce, Maurizio, Perrino, Cinzia, Prunier, Fabrice, Van Linthout, Sophie, Ytrehus, Kirsti, Zimmermann, Wolfram-Hubertus, Ferdinandy, Peter, and Sluijter, Joost P G

Subjects
Biomaterials, Ischaemic heart disease, Physiology, Cells, Physiology (medical), Journal Article, Heart failure, Cardiac tissue engineering, Cardiology and Cardiovascular Medicine
Abstract

Morbidity and mortality from ischaemic heart disease (IHD) and heart failure (HF) remain significant in Europe and are increasing worldwide. Patients with IHD or HF might benefit from novel therapeutic strategies, such as cell-based therapies. We recently discussed the therapeutic potential of cell-based therapies and provided recommendations on how to improve the therapeutic translation of these novel strategies for effective cardiac regeneration and repair. Despite major advances in optimizing these strategies with respect to cell source and delivery method, the clinical outcome of cell-based therapy remains unsatisfactory. Major obstacles are the low engraftment and survival rate of transplanted cells in the harmful microenvironment of the host tissue, and the paucity or even lack of endogenous cells with repair capacity. Therefore, new ways of delivering cells and their derivatives are required in order to empower cell-based cardiac repair and regeneration in patients with IHD or HF. Strategies using tissue engineering (TE) combine cells with matrix materials to enhance cell retention or cell delivery in the transplanted area, and have recently received much attention for this purpose. Here, we summarize knowledge on novel approaches emerging from the TE scenario. In particular, we will discuss how combinations of cell/bio-materials (e.g. hydrogels, cell sheets, prefabricated matrices, microspheres, and injectable matrices) combinations might enhance cell retention or cell delivery in the transplantation areas, thereby increase the success rate of cell therapies for IHD and HF. We will not focus on the use of classical engineering approaches, employing fully synthetic materials, because of their unsatisfactory material properties which render them not clinically applicable. The overall aim of this Position Paper from the ESC Working Group Cellular Biology of the Heart is to provide recommendations on how to proceed in research with these novel TE strategies combined with cell-based therapies to boost cardiac repair in the clinical settings of IHD and HF.

Published
2019

46. ESC Working Group on Cellular Biology of the Heart:Tissue Engineering and Cell-Based Therapies for Cardiac Repair in Ischemic Heart Disease and Heart Failure

Author

Madonna, Rosalinda, Van Laake, Linda W, Botker, Hans Erik, Davidson, Sean M, De Caterina, Raffaele, Engel, Felix B, Eschenhagen, Thomas, Fernandez-Aviles, Francesco, Hausenloy, Derek J, Hulot, Jean-Sebastien, Lecour, Sandrine, Leor, Jonathan, Menasché, Philippe, Pesce, Maurizio, Perrino, Cinzia, Prunier, Fabrice, Van Linthout, Sophie, Ytrehus, Kirsti, Zimmermann, Wolfram-Hubertus, Ferdinandy, Peter, and Sluijter, Joost P G

Abstract

Morbidity and mortality from ischemic heart disease (IHD) and heart failure (HF) remain significant in Europe and are increasing worldwide. Patients with IHD or HF might benefit from novel therapeutic strategies, such as cell-based therapies. We recently discussed the therapeutic potential of cell-based therapies and provided recommendations on how to improve the therapeutic translation of these novel strategies for effective cardiac regeneration and repair. Despite major advances in optimizing these strategies with respect to cell source and delivery method, the clinical outcome of cell-based therapy remains unsatisfactory. Major obstacles are the low engraftment and survival rate of transplanted cells in the harmful microenvironment of the host tissue, and the paucity or even lack of endogenous cells with repair capacity. Therefore, new ways of delivering cells and their derivatives are required in order to empower cell-based cardiac repair and regeneration in patients with IHD or HF. Strategies using tissue engineering (TE) combine cells with matrix materials to enhance cell retention or cell delivery in the transplanted area, and have recently received much attention for this purpose. Here, we summarize knowledge on novel approaches emerging from the TE scenario. In particular, we will discuss how combinations of cell/bio-materials (e.g., hydrogels, cell sheets, prefabricated matrices, microspheres, and injectable matrices) combinations might enhance cell retention or cell delivery in the transplantation areas and thereby increase the success rate of cell therapies for IHD and HF. We will not focus on the use of classical engineering approaches, employing fully synthetic materials, because of their unsatisfactory material properties which render them not clinically applicable. The overall aim of this Position Paper from the ESC Working Group Cellular Biology of the Heart is to provide recommendations on how to proceed in research with these novel tissue engineering strategies combined with cell-based therapies to boost cardiac repair in the clinical settings of IHD and HF.

Published
2019
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49. Functional genomics meta-analysis to identify gene set enrichment networks in cardiac hypertrophy.

Author

Angeloni, Miriam, Thievessen, Ingo, Engel, Felix B., Magni, Paolo, and Ferrazzi, Fulvia

Subjects
CARDIAC hypertrophy, FUNCTIONAL genomics, TISSUE remodeling, ENERGY metabolism, GENES, BIOLOGICAL networks
Abstract

In order to take advantage of the continuously increasing number of transcriptome studies, it is important to develop strategies that integrate multiple expression datasets addressing the same biological question to allow a robust analysis. Here, we propose a meta-analysis framework that integrates enriched pathways identified through the Gene Set Enrichment Analysis (GSEA) approach and calculates for each meta-pathway an empirical p-value. Validation of our approach on benchmark datasets showed comparable or even better performance than existing methods and an increase in robustness with increasing number of integrated datasets. We then applied the meta-analysis framework to 15 functional genomics datasets of physiological and pathological cardiac hypertrophy. Within these datasets we grouped expression sets measured at time points that represent the same hallmarks of heart tissue remodeling ('aggregated time points') and performed meta-analysis on the expression sets assigned to each aggregated time point. To facilitate biological interpretation, results were visualized as gene set enrichment networks. Here, our meta-analysis framework identified well-known biological mechanisms associated with pathological cardiac hypertrophy (e.g., cardiomyocyte apoptosis, cardiac contractile dysfunction, and alteration in energy metabolism). In addition, results highlighted novel, potentially cardioprotective mechanisms in physiological cardiac hypertrophy involving the down-regulation of immune cell response, which are worth further investigation. [ABSTRACT FROM AUTHOR]

Published
2021
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50. PPARβ/δ: Linking Metabolism to Regeneration

Author

Magadum, Ajit and Engel, Felix B.

Subjects
proliferation, Akt, differentiation, glycolysis, Wnt signaling, lcsh:Chemistry, PPARβ/δ, lcsh:Biology (General), lcsh:QD1-999, Medizinische Fakultät, PDK1, regeneration, ddc:610, metabolism, lcsh:QH301-705.5
Abstract

In contrast to the general belief that regeneration is a rare event, mainly occurring in simple organisms, the ability of regeneration is widely distributed in the animal kingdom. Yet, the efficiency and extent of regeneration varies greatly. Humans can recover from blood loss as well as damage to tissues like bone and liver. Yet damage to the heart and brain cannot be reversed, resulting in scaring. Thus, there is a great interest in understanding the molecular mechanisms of naturally occurring regeneration and to apply this knowledge to repair human organs. During regeneration, injury-activated immune cells induce wound healing, extracellular matrix remodeling, migration, dedifferentiation and/or proliferation with subsequent differentiation of somatic or stem cells. An anti-inflammatory response stops the regenerative process, which ends with tissue remodeling to achieve the original functional state. Notably, many of these processes are associated with enhanced glycolysis. Therefore, peroxisome proliferator-activated receptor (PPAR) β/δ—which is known to be involved for example in lipid catabolism, glucose homeostasis, inflammation, survival, proliferation, differentiation, as well as mammalian regeneration of the skin, bone and liver—appears to be a promising target to promote mammalian regeneration. This review summarizes our current knowledge of PPARβ/δ in processes associated with wound healing and regeneration.

Published
2018

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