4.8 Article

Functional redundancy of type I and type II receptors in the regulation of skeletal muscle growth by myostatin and activin A

出版社

NATL ACAD SCIENCES
DOI: 10.1073/pnas.2019263117

关键词

myostatin; activin; receptors; skeletal muscle

资金

  1. NIH [R01AR060636, R01AG052962]
  2. UConn Health
  3. Connecticut Children's

向作者/读者索取更多资源

Myostatin (MSTN) is a transforming growth factor -I3 (TGF-I3) family member that normally acts to limit muscle growth. The function of MSTN is partially redundant with that of another TGF-I3 family member, activin A. MSTN and activin A are capable of signaling through a complex of type II and type I receptors. Here, we investigated the roles of two type II receptors (ACVR2 and ACVR2B) and two type I receptors (ALK4 and ALK5) in the regulation of muscle mass by these ligands by genetically targeting these receptors either alone or in combination specifically in myofibers in mice. We show that targeting signaling in myofibers is sufficient to cause significant increases in muscle mass, showing that myofibers are the direct target for signaling by these ligands in the regulation of muscle growth. Moreover, we show that there is functional redundancy between the two type II receptors as well as between the two type I receptors and that all four type II/type I receptor combinations are utilized in vivo. Targeting signaling specifically in myofibers also led to reductions in overall body fat content and improved glucose metabolism in mice fed either regular chow or a high-fat diet, demonstrating that these metabolic effects are the result of enhanced muscling. We observed no effect, however, on either bone density or muscle regeneration in mice in which signaling was targeted in myofibers. The latter finding implies that MSTN likely signals to other cells, such as satellite cells, in addition to myofibers to regulate muscle homeostasis.

作者

我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。

评论

主要评分

4.8
评分不足

次要评分

新颖性
-
重要性
-
科学严谨性
-
评价这篇论文

推荐

暂无数据
暂无数据