期刊
JOURNAL OF BIOLOGICAL CHEMISTRY
卷 292, 期 38, 页码 15939-15951出版社
ELSEVIER
DOI: 10.1074/jbc.M117.785709
关键词
-
资金
- Scientific Research on Innovative Areas [23112007]
- Ministry of Education, Culture, Sports, Science and Technology, Japan [26670157]
- [15K18968]
- [17K15596]
- [16H05152]
- Grants-in-Aid for Scientific Research [26670157, 16H05152, 26253057, 15H04352, 17H06421] Funding Source: KAKEN
The Ror family receptor tyrosine kinases, Ror1 and Ror2, play important roles in regulating developmental morphogenesis and tissue-and organogenesis, but their roles in tissue regeneration in adult animals remain largely unknown. In this study, we examined the expression and function of Ror1 and Ror2 during skeletal muscle regeneration. Using an in vivo skeletal muscle injury model, we show that expression of Ror1 and Ror2 in skeletal muscles is induced transiently by the inflammatory cytokines, TNF-alpha and IL-1 beta, after injury and that inhibition of TNF-alpha and IL-1 beta by neutralizing antibodies suppresses expression of Ror1 and Ror2 in injured muscles. Importantly, expression of Ror1, but not Ror2, was induced primarily in Pax7-positive satellite cells (SCs) after muscle injury, and administration of neutralizing antibodies decreased the proportion of Pax7positive proliferative SCs after muscle injury. We also found that stimulation of a mouse myogenic cell line, C2C12 cells, with TNF-alpha or IL-1 beta induced expression of Ror1 via NF-kappa B activation and that suppressed expression of Ror1 inhibited their proliferative responses in SCs. Intriguingly, SC-specific depletion of Ror1 decreased the number of Pax7-positive SCs after muscle injury. Collectively, these findings indicate for the first time that Ror1 has a critical role in regulating SC proliferation during skeletal muscle regeneration. Weconclude that Ror1 might be a suitable target in the development of diagnostic and therapeutic approaches to manage muscular disorders.
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。
推荐
暂无数据