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- Title
HEXIM1 controls satellite cell expansion after injury to regulate skeletal muscle regeneration.
- Authors
Peng Hong; Kang Chen; Bihui Huang; Min Liu; Miao Cui; Rozenberg, Inna; Chaqour, Brahim; Pan, Xiaoyue; Barton, Elisabeth R.; Xian-Cheng Jiang; Siddiqui, M. A. Q.
- Abstract
The native capacity of adult skeletal muscles to regenerate is vital to the recovery from physical injuries and dystrophic diseases. Currently, the development of therapeutic interventions has been hindered by the com-plex regulatory network underlying the process of muscle regeneration. Using a mouse model of skeletal mus-cle regeneration after injury, we identified hexamethylene bisacetamide inducible 1 (HEXIM1, also referred to as CLP-1), the inhibitory component of the positive transcription elongation factor b (P-TEFb) complex, as a pivotal regulator of skeletal muscle regeneration. Heximl-haplodeficient muscles exhibited greater mass and preserved function compared with those of WT muscles after injury, as a result of enhanced expansion of satellite cells. Transplanted Heximl -haplodeficient satellite cells expanded and improved muscle regeneration more effectively than WT satellite cells. Conversely, HEXIM1 overexpression restrained satellite cell prolifer-ation and impeded muscle regeneration. Mechanistically, dissociation of HEXIM1 from P-TEFb and subse-quent activation of P-TEFb are required for satellite cell proliferation and the prevention of early myogenic differentiation. These findings suggest a crucial role for the HEXIMl/P-TEFb pathway in the regulation of satellite cell-mediated muscle regeneration and identify HEXIM1 as a potential therapeutic target for degen-erative muscular diseases.
- Publication
Journal of Clinical Investigation, 2012, Vol 122, Issue 11, p3873
- ISSN
0021-9738
- Publication type
Academic Journal
- DOI
10.1172/JCI62818