%A Jiao Meng,Xiaoting Zou,Rimao Wu,Ran Zhong,Dahai Zhu,Yong Zhang %T Accelerated regeneration of the skeletal muscle in RNF13-knockout mice is mediated by macrophage-secreted IL-4/IL-6 %0 Journal Article %D 2014 %J Protein Cell %J Protein & Cell %@ 1674-800X %R 10.1007/s13238-014-0025-4 %P 235-247 %V 5 %N 3 %U {https://journal.hep.com.cn/pac/EN/10.1007/s13238-014-0025-4 %8 2014-06-23 %X

RING finger protein 13 (RNF13) is a newly identified E3 ligase reported to be functionally significant in the regulation of cancer development, muscle cell growth, and neuronal development. In this study, the function of RNF13 in cardiotoxin-induced skeletal muscle regeneration was investigated using RNF13-knockout mice. RNF13-/- mice exhibited enhanced muscle regeneration —characterized by accelerated satellite cell proliferation —compared with wild-type mice. The expression of RNF13 was remarkably induced in macrophages rather than in the satellite cells of wild-type mice at the very early stage of muscle damage. This result indicated that inflammatory cells are important in RNF13-mediated satellite cell functions. The cytokine levels in skeletal muscles were further analyzed and showed that RNF13-/- mice produced greater amounts of various cytokines than wild-type mice. Among these, IL-4 and IL-6 levels significantly increased in RNF13-/- mice. The accelerated muscle regeneration phenotype was abrogated by inhibiting IL-4/IL-6 action in RNF13-/- mice with blocking antibodies. These results indicate that RNF13 deficiency promotes skeletal muscle regeneration via the effects on satellite cell niche mediated by IL-4 and IL-6.