心外膜FSTL1重建可使成年哺乳动物心脏再生。
Epicardial FSTL1 reconstitution regenerates the adult mammalian heart.
作者信息
Wei Ke, Serpooshan Vahid, Hurtado Cecilia, Diez-Cuñado Marta, Zhao Mingming, Maruyama Sonomi, Zhu Wenhong, Fajardo Giovanni, Noseda Michela, Nakamura Kazuto, Tian Xueying, Liu Qiaozhen, Wang Andrew, Matsuura Yuka, Bushway Paul, Cai Wenqing, Savchenko Alex, Mahmoudi Morteza, Schneider Michael D, van den Hoff Maurice J B, Butte Manish J, Yang Phillip C, Walsh Kenneth, Zhou Bin, Bernstein Daniel, Mercola Mark, Ruiz-Lozano Pilar
机构信息
Department of Bioengineering, University of California, San Diego, La Jolla, California 92037, USA.
Sanford-Burnham-Prebys Medical Discovery Institute, 10901 N. Torrey Pines Road, La Jolla, California 92037, USA.
出版信息
Nature. 2015 Sep 24;525(7570):479-85. doi: 10.1038/nature15372. Epub 2015 Sep 16.
The elucidation of factors that activate the regeneration of the adult mammalian heart is of major scientific and therapeutic importance. Here we found that epicardial cells contain a potent cardiogenic activity identified as follistatin-like 1 (Fstl1). Epicardial Fstl1 declines following myocardial infarction and is replaced by myocardial expression. Myocardial Fstl1 does not promote regeneration, either basally or upon transgenic overexpression. Application of the human Fstl1 protein (FSTL1) via an epicardial patch stimulates cell cycle entry and division of pre-existing cardiomyocytes, improving cardiac function and survival in mouse and swine models of myocardial infarction. The data suggest that the loss of epicardial FSTL1 is a maladaptive response to injury, and that its restoration would be an effective way to reverse myocardial death and remodelling following myocardial infarction in humans.
阐明激活成年哺乳动物心脏再生的因素具有重大的科学和治疗意义。我们在此发现，心外膜细胞含有一种被鉴定为卵泡抑素样1（Fstl1）的强大心脏发生活性。心肌梗死后心外膜Fstl1减少，并被心肌表达所取代。心肌Fstl1无论是在基础状态还是转基因过表达时都不会促进再生。通过心外膜贴片应用人Fstl1蛋白（FSTL1）可刺激已存在的心肌细胞进入细胞周期并分裂，改善心肌梗死小鼠和猪模型的心脏功能和存活率。数据表明，心外膜FSTL1的丧失是对损伤的一种适应不良反应，其恢复将是逆转人类心肌梗死后心肌死亡和重塑的有效方法。
Zotero 插件