Cardiovascular Research Institute, University of California, San Francisco, San Francisco, CA 94143, USA.
Duke Regeneration Center, Department of Cell Biology, Duke University School of Medicine, Durham, NC 27710, USA.
Sci Adv. 2023 Dec;9(48):eadh5313. doi: 10.1126/sciadv.adh5313. Epub 2023 Nov 29.
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.
哺乳动物的心脏再生能力有限，而斑马鱼具有非凡的再生能力。在斑马鱼心脏再生过程中，内皮细胞促进心肌细胞细胞周期再进入和心肌修复，但促进有利于再生的损伤微环境的机制仍不完全明确。在这里，我们确定基质金属蛋白酶 Mmp14b 是心脏再生的重要调节因子。我们在斑马鱼和小鼠中鉴定出一个由心脏损伤诱导的 TEAD 依赖性内皮增强子，我们表明该增强子是再生所必需的，支持 Hippo 信号通路在上游的作用。最后，我们表明，MMP-14 在小鼠中的功能对于 Agrin 的积累很重要，Agrin 是新生小鼠心脏再生的重要调节因子。这些发现揭示了促进心脏再生的细胞外基质重塑机制。
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