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新闻资讯

细胞外基质Agrin能促进小鼠心脏再生

发布时间:2017-07-17 浏览次数:741

信息来源:
http://www.natureasia.com/zh-cn/nature/highlights/87364
https://www.nature.com/nature/journal/v547/n7662/full/nature22978.html

新生小鼠心脏在小鼠出生后的有限时间内可以再生,但是这种特性很快就会丧失。Eldad Tzahor及同事鉴定了新生心脏细胞外基质的一个组分——Agrin,它是新生小鼠心脏再生所必需的。他们进一步表明,重组Agrin可用于改善经历心肌梗塞后的成年小鼠的心脏功能。Agrin改进心脏功能、促进心脏再生的机制可能是多方面的,但是作者也表明该机制能促进心肌细胞增殖,这或许是研究人员观察到前述效应的原因。

The extracellular matrix protein agrin promotes heart regeneration in mice

Elad Bassat,Yara Eid Mutlak,Alex Genzelinakh,Ilya Y. Shadrin,Kfir Baruch Umansky, Oren Yifa,David Kain, Dana Rajchman,John Leach,Daria Riabov Bassat,Yael Udi,Rachel Sarig, Irit Sagi,James F. Martin,Nenad Bursac, Shenhav Cohen & Eldad Tzahor

Nature 547, 179–184 (13 July 2017) doi:10.1038/nature22978

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.