An injury-responsive mmp14b enhancer is required for heart regeneration.

Autor: Zlatanova I; Cardiovascular Research Institute, University of California, San Francisco, San Francisco, CA 94143, USA., Sun F; Duke Regeneration Center, Department of Cell Biology, Duke University School of Medicine, Durham, NC 27710, USA., Wu RS; Cardiovascular Research Institute, University of California, San Francisco, San Francisco, CA 94143, USA., Chen X; Cardiovascular Research Institute, University of California, San Francisco, San Francisco, CA 94143, USA., Lau BH; Cardiovascular Research Institute, University of California, San Francisco, San Francisco, CA 94143, USA., Colombier P; Cardiovascular Research Institute, University of California, San Francisco, San Francisco, CA 94143, USA., Sinha T; Cardiovascular Research Institute, University of California, San Francisco, San Francisco, CA 94143, USA., Celona B; Cardiovascular Research Institute, University of California, San Francisco, San Francisco, CA 94143, USA., Xu SM; Cardiovascular Research Institute, University of California, San Francisco, San Francisco, CA 94143, USA., Materna SC; Cardiovascular Research Institute, University of California, San Francisco, San Francisco, CA 94143, USA., Huang GN; Cardiovascular Research Institute, University of California, San Francisco, San Francisco, CA 94143, USA.; Department of Physiology, University of California, San Francisco, San Francisco, CA 94143, USA., Black BL; Cardiovascular Research Institute, University of California, San Francisco, San Francisco, CA 94143, USA.; Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA 94143, USA.
Jazyk: angličtina
Zdroj: Science advances [Sci Adv] 2023 Dec; Vol. 9 (48), pp. eadh5313. Date of Electronic Publication: 2023 Nov 29.
DOI: 10.1126/sciadv.adh5313
Abstrakt: 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.
Databáze: MEDLINE
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