細胞外基質Agrin能促進小鼠心臟再生

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

新生小鼠心臟在小鼠出生后的有限時間內可以再生,但是這種特性很快就會喪失。Eldad Tzahor及同事鑒定了新生心臟細胞外基質的一個組分——Agrin,它是新生小鼠心臟再生所必需的。他們進一步表明,重組Agrin可用于改善經歷心肌梗塞后的成年小鼠的心臟功能。Agrin改進心臟功能、促進心臟再生的機制可能是多方面的,但是作者也表明該機制能促進心肌細胞增殖,這或許是研究人員觀察到前述效應的原因。

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.

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