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ZFIN ID: ZDB-PUB-191202-2
TGF-β Signaling Promotes Tissue Formation during Cardiac Valve Regeneration in Adult Zebrafish
Bensimon-Brito, A., Ramkumar, S., Boezio, G.L.M., Guenther, S., Kuenne, C., Helker, C.S.M., Sánchez-Iranzo, H., Iloska, D., Piesker, J., Pullamsetti, S., Mercader, N., Beis, D., Stainier, D.Y.R.
Date: 2019
Source: Developmental Cell   52(1): 9-20.e7 (Journal)
Registered Authors: Beis, Dimitris, Helker, Christian, Mercader Huber, Nadia, Stainier, Didier
Keywords: atrio-ventricular, cell ablation, cell tracing, cell transplantation, endothelium, extracellular matrix, laser capture microdissection, valve endothelial cells, valve interstitial cells, whole kidney marrow
Microarrays: GEO:GSE136786
MeSH Terms:
  • Animals
  • Cell Cycle
  • Cell Differentiation*
  • Endothelium/cytology*
  • Endothelium/metabolism
  • Extracellular Matrix/metabolism
  • Heart Valves/cytology*
  • Heart Valves/metabolism
  • Kidney/cytology*
  • Kidney/metabolism
  • Models, Animal
  • Regeneration*
  • Tissue Engineering/methods
  • Transforming Growth Factor beta/metabolism*
  • Zebrafish/growth & development*
  • Zebrafish/metabolism
PubMed: 31786069 Full text @ Dev. Cell
Cardiac valve disease can lead to severe cardiac dysfunction and is thus a frequent cause of morbidity and mortality. Its main treatment is valve replacement, which is currently greatly limited by the poor recellularization and tissue formation potential of the implanted valves. As we still lack suitable animal models to identify modulators of these processes, here we used adult zebrafish and found that, upon valve decellularization, they initiate a rapid regenerative program that leads to the formation of new functional valves. After injury, endothelial and kidney marrow-derived cells undergo cell cycle re-entry and differentiate into new extracellular matrix-secreting valve cells. The TGF-β signaling pathway promotes the regenerative process by enhancing progenitor cell proliferation as well as valve cell differentiation. These findings reveal a key role for TGF-β signaling in cardiac valve regeneration and establish the zebrafish as a model to identify and test factors promoting cardiac valve recellularization and growth.