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Cardiac valve regeneration in adult zebrafish: importance of TGF-β signaling in new tissue formation [article]

Anabela Bensimon-Brito, Srinath Ramkumar, Giulia L. M. Boezio, Stefan Guenther, Carsten Kuenne, Hector Sanchez-Iranzo, Dijana Iloska, Janett Piesker, Soni Pullamsetti, Nadia Mercader, Dimitris Beis, Didier Y. R. Stainier
2019 bioRxiv   pre-print
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 the adult zebrafish and found that, upon valve decellularization, they initiate a striking regenerative program that leads
more » ... 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 Transforming Growth Factor beta (TGFβ) signaling pathway promotes this process by enhancing progenitor cell proliferation as well as valve cell differentiation. These findings reveal a key role for TGFβ signaling in valve regeneration and also establish the zebrafish as a model to identify and test factors promoting valve recellularization and growth.
doi:10.1101/697706 fatcat:h25yhy6cfzc5bixu26qwcsoxuq