An injury-responsivemmp14benhancer is required for heart regeneration

作者：Ivana Zlatanova, Fei Sun, Roland S. Wu, X Chen, Bryan H. Lau, Pauline Colombier, Tanvi Sinha, Barbara Celona, Shan-Mei Xu, Stefan C. Materna, Guo N. Huang, Brian L. Black · 发表于：Science Advances · 年份：2023 · DOI：10.1126/sciadv.adh5313 · 被引用次数：28 · 研究领域：Hippo pathway signaling and YAP/TAZ、Congenital heart defects research、Ubiquitin and proteasome pathways

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 mmp14b 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 mmp14b . 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.