An injury-responsive mmp14b enhancer is required for heart regeneration

• Published in: Science advances Vol. 9; no. 48; p. eadh5313
• Main Authors: Zlatanova, Ivana, Sun, Fei, Wu, Roland S, Chen, Xiaoxin, Lau, Bryan H, Colombier, Pauline, Sinha, Tanvi, Celona, Barbara, Xu, Shan-Mei, Materna, Stefan C, Huang, Guo N, Black, Brian L
• Format: Journal Article
• Language: English
• Published: United States American Association for the Advancement of Science 01.12.2023
• Subjects: Animals; Biomedicine and Life Sciences; Cell Proliferation; Endothelial Cells; Mammals; Mice; Myocardium - metabolism; Myocytes, Cardiac - metabolism; Regeneration; SciAdv r-articles; Zebrafish
• ISSN: 2375-2548; 2375-2548
• DOI: 10.1126/sciadv.adh5313

Mammals have limited capacity for heart regeneration, whereas zebrafish have extraordinary regeneration abilities. During zebrafish heart regeneration, endothelial cells promote cardiomyocyte cell cycle reentry and myocardial repair, but the mechanisms responsible for promoting an injury microenvironment conducive to regeneration remain incompletely defined. Here, we identify the matrix metalloproteinase Mmp14b as an essential regulator of heart regeneration. We identify a TEAD-dependent endothelial enhancer induced by heart injury in zebrafish and mice, and we show that the enhancer is required for regeneration, supporting a role for Hippo signaling upstream of . Last, we show that MMP-14 function in mice is important for the accumulation of Agrin, an essential regulator of neonatal mouse heart regeneration. These findings reveal mechanisms for extracellular matrix remodeling that promote heart regeneration.