Accelerated regeneration of the skeletal muscle in RNF13-knockout mice is mediated by macrophage-secreted IL-4/IL-6.
10.1007/s13238-014-0025-4
- Author:
Jiao MENG
1
;
Xiaoting ZOU
;
Rimao WU
;
Ran ZHONG
;
Dahai ZHU
;
Yong ZHANG
Author Information
1. The National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and School of Basic Medicine, Peking Union Medical College, Beijing, 100005, China.
- Publication Type:Journal Article
- MeSH:
Animals;
Cell Proliferation;
Inflammation;
pathology;
Interleukin-4;
metabolism;
Interleukin-6;
metabolism;
Macrophages;
metabolism;
Mice;
Mice, Knockout;
Muscle, Skeletal;
metabolism;
pathology;
physiopathology;
Regeneration;
Satellite Cells, Skeletal Muscle;
metabolism;
pathology;
Ubiquitin-Protein Ligases;
deficiency;
metabolism
- From:
Protein & Cell
2014;5(3):235-247
- CountryChina
- Language:English
-
Abstract:
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.
