文章基本信息

标题：Angiotensin II receptor blockade promotes repair of skeletal muscle through down-regulation of aging-promoting C1q expression
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作者：Chizuru Yabumoto ; Hiroshi Akazawa ; Rie Yamamoto 等
期刊名称：Scientific Reports
电子版ISSN：2045-2322
出版年度：2015
卷号：5
期号：1
DOI：10.1038/srep14453
语种：English
出版社：Springer Nature
摘要：Disruption of angiotensin II type 1 (AT₁) receptor prolonged life span in mice. Since aging-related decline in skeletal muscle function was retarded in Atgr1a ^−/− mice, we examined the role of AT₁ receptor in muscle regeneration after injury. Administration of AT₁ receptor blocker irbesartan increased the size of regenerating myofibers, decreased fibrosis, and enhanced functional muscle recovery after cryoinjury. We recently reported that complement C1q, secreted by macrophages, activated Wnt/β-catenin signaling and promoted aging-related decline in regenerative capacity of skeletal muscle. Notably, irbesartan induced M2 polarization of macrophages, but reduced C1q expression in cryoinjured muscles and in cultured macrophage cells. Irbesartan inhibited up-regulation of Axin 2, a downstream gene of Wnt/β-catenin pathway, in cryoinjured muscles. In addition, topical administration of C1q reversed beneficial effects of irbesartan on skeletal muscle regeneration after injury. These results suggest that AT₁ receptor blockade improves muscle repair and regeneration through down-regulation of the aging-promoting C1q-Wnt/β-catenin signaling pathway.