title: Accelerated regeneration of the skeletal muscle in RNF13-knockout mice is mediated by macrophage-secreted IL-4/IL-6.
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.
authors.affiliation: 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.
authors.forename: Jiao
authors.initials: J
authors.lastname: Meng
authors.forename: Xiaoting
authors.initials: X
authors.lastname: Zou
authors.forename: Rimao
authors.initials: R
authors.lastname: Wu
authors.forename: Ran
authors.initials: R
authors.lastname: Zhong
authors.forename: Dahai
authors.initials: D
authors.lastname: Zhu
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D007249:Inflammation / Q000473:pathology; D015847:Interleukin-4 / Q000378:metabolism*; D015850:Interleukin-6 / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D012038:Regeneration; D032496:Satellite Cells, Skeletal Muscle / Q000378:metabolism / Q000473:pathology; D044767:Ubiquitin-Protein Ligases / Q000172:deficiency* / Q000378:metabolism
chemical_list: D015850:Interleukin-6; D015847:Interleukin-4; C539844:RNF13 protein, mouse; D044767:Ubiquitin-Protein Ligases