文章基本信息

标题：COMP-Angiopoietin-1 accelerates muscle regeneration through N-cadherin activation
本地全文：下载
作者：Seock-Won Youn ; Hyun-Chae Lee ; Sae-Won Lee 等
期刊名称：Scientific Reports
电子版ISSN：2045-2322
出版年度：2018
卷号：8
期号：1
页码：12323
DOI：10.1038/s41598-018-30513-7
语种：English
出版社：Springer Nature
摘要：Angiopoietin-1 modulates vascular stability via Tie2 on endothelial cells. In our previous study, we also showed it acts as an inhibitor of cardiomyocyte death. However, it remains poorly understood how Ang1 regulates myogenesis during muscle regeneration. Here we found that COMP-Ang1 (cAng1) enhances muscle regeneration through N-cadherin activation. Muscle fiber regeneration after limb muscle damage by ischemic injury was enhanced with cAng1 treatment. Mechanistically cAng1 directly bound to N-cadherin on the myoblast surface in a Ca²⁺ dependent manner. The interaction enhanced N-cadherin activation via N-cadherin/p120-catenin complex formation, which in turn activated p38MAPK (but not AKT or ERK) and myogenin expression (but not myoD) as well as increasing myogenin⁺ cells in/ex vivo . After transplantation of GFP-expressing myoblasts (GFP-MB), we showed an increased generation of GFP⁺ myotubes with adenovirus cAng1 (Adv-cAng1) injection. Adv-cAng1, however, could not stimulate myotube formation in N-cadherin-depleted GFP-MB. Taken together, this study uncovers the mechanism of how cAng1 promotes myoblast differentiation and muscle regeneration through the N-cadherin/p120-catenin/p38MAPK/myogenin axis.