疤痕
整合素
胶原受体
机械敏感通道
生物
胶原VI
心肌梗塞
成纤维细胞
表型
细胞外基质
瘢痕组织
病理
Ⅰ型胶原
细胞生物学
内科学
内分泌学
医学
外科
细胞
受体
体外
遗传学
基因
离子通道
作者
Tomohiro Yokota,Jackie L. McCourt,Feiyang Ma,Shuxun Ren,Shen Li,Tae‐Hyung Kim,Yerbol Z. Kurmangaliyev,Rohollah Nasiri,Samad Ahadian,Thang L. Nguyen,Xing Haw Marvin Tan,Yonggang Zhou,Rimao Wu,A. Domínguez Rodríguez,Whitaker Cohn,Yibin Wang,Julian P. Whitelegge,Sergey Ryazantsev,Ali Khademhosseini,Michael A. Teitell
出处
期刊:Cell
[Cell Press]
日期:2020-07-03
卷期号:182 (3): 545-562.e23
被引量:160
标识
DOI:10.1016/j.cell.2020.06.030
摘要
Scar tissue size following myocardial infarction is an independent predictor of cardiovascular outcomes, yet little is known about factors regulating scar size. We demonstrate that collagen V, a minor constituent of heart scars, regulates the size of heart scars after ischemic injury. Depletion of collagen V led to a paradoxical increase in post-infarction scar size with worsening of heart function. A systems genetics approach across 100 in-bred strains of mice demonstrated that collagen V is a critical driver of postinjury heart function. We show that collagen V deficiency alters the mechanical properties of scar tissue, and altered reciprocal feedback between matrix and cells induces expression of mechanosensitive integrins that drive fibroblast activation and increase scar size. Cilengitide, an inhibitor of specific integrins, rescues the phenotype of increased post-injury scarring in collagen-V-deficient mice. These observations demonstrate that collagen V regulates scar size in an integrin-dependent manner.
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