The extracellular matrix protein agrin promotes heart regeneration in mice

被引：565

作者：

Bassat, Elad ^{[1
]}

Mutlak, Yara Eid ^{[2
]}

Genzelinakh, Alex ^{[1
]}

Shadrin, Ilya Y. ^{[3
]}

Umansky, Kfir Baruch ^{[1
]}

Yifa, Oren ^{[1
]}

Kain, David ^{[1
]}

Rajchman, Dana ^{[1
]}

Leach, John ^{[4
,5
]}

Bassat, Daria Riabov ^{[6
]}

Udi, Yael ^{[6
]}

Sarig, Rachel ^{[1
]}

Sagi, Irit ^{[6
]}

Martin, James F. ^{[4
,5
]}

Bursac, Nenad ^{[3
]}

Cohen, Shenhav ^{[2
]}

Tzahor, Eldad ^{[1
]}

机构：

[1] Weizmann Inst Sci, Dept Mol Cell Biol, IL-76100 Rehovot, Israel

[2] Technion, Fac Biol, IL-32000 Haifa, Israel

[3] Duke Univ, Dept Biomed Engn, Durham, NC 27708 USA

[4] Baylor Coll Med, Houston, TX 77030 USA

[5] Texas Heart Inst, Houston, TX 77030 USA

[6] Weizmann Inst Sci, Dept Regulat Biol, IL-76100 Rehovot, Israel

来源：

NATURE | 2017年 / 547卷 / 7662期

基金：

以色列科学基金会; 欧洲研究理事会;

关键词：

RECEPTOR; CARDIOMYOCYTES; IDENTIFICATION; PROLIFERATION; DYSTROGLYCAN; MATURATION; BINDING;

D O I：

10.1038/nature22978

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];

摘要：

The adult mammalian heart is non-regenerative owing to the post-mitotic nature of cardiomyocytes. The neonatal mouse heart can regenerate, but only during the first week of life. Here we show that changes in the composition of the extracellular matrix during this week can affect cardiomyocyte growth and differentiation in mice. We identify agrin, a component of neonatal extracellular matrix, as required for the full regenerative capacity of neonatal mouse hearts. In vitro, recombinant agrin promotes the division of cardiomyocytes that are derived from mouse and human induced pluripotent stem cells through a mechanism that involves the disassembly of the dystrophin-glycoprotein complex, and Yap-and ERK-mediated signalling. In vivo, a single administration of agrin promotes cardiac regeneration in adult mice after myocardial infarction, although the degree of cardiomyocyte proliferation observed in this model suggests that there are additional therapeutic mechanisms. Together, our results uncover a new inducer of mammalian heart regeneration and highlight fundamental roles of the extracellular matrix in cardiac repair.

引用

页码：179 / +

页数：17

共 30 条

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