Document Detail


HEXIM1 controls satellite cell expansion after injury to regulate skeletal muscle regeneration.
MedLine Citation:
PMID:  23023707     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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 complex regulatory network underlying the process of muscle regeneration. Using a mouse model of skeletal muscle 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. Hexim1-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 Hexim1-haplodeficient satellite cells expanded and improved muscle regeneration more effectively than WT satellite cells. Conversely, HEXIM1 overexpression restrained satellite cell proliferation and impeded muscle regeneration. Mechanistically, dissociation of HEXIM1 from P-TEFb and subsequent 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 HEXIM1/P-TEFb pathway in the regulation of satellite cell–mediated muscle regeneration and identify HEXIM1 as a potential therapeutic target for degenerative muscular diseases.
Authors:
Peng Hong; Kang Chen; Bihui Huang; Min Liu; Miao Cui; Inna Rozenberg; Brahim Chaqour; Xiaoyue Pan; Elisabeth R Barton; Xian-Cheng Jiang; M A Q Siddiqui
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The Journal of clinical investigation     Volume:  122     ISSN:  1558-8238     ISO Abbreviation:  J. Clin. Invest.     Publication Date:  2012 Nov 
Date Detail:
Created Date:  2012-12-26     Completed Date:  2013-01-15     Revised Date:  2013-09-18    
Medline Journal Info:
Nlm Unique ID:  7802877     Medline TA:  J Clin Invest     Country:  United States    
Other Details:
Languages:  eng     Pagination:  3873-87     Citation Subset:  AIM; IM    
Affiliation:
Department of Cell Biology, State University of New York Downstate Medical Center,New York, New York, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Cell Differentiation / physiology*
Cell Proliferation
Mice
Mice, Mutant Strains
Muscle Proteins / genetics,  metabolism*
Muscle, Skeletal / injuries*,  metabolism*
Positive Transcriptional Elongation Factor B / metabolism
Regeneration / physiology*
Satellite Cells, Skeletal Muscle / metabolism*
Transcription Factors / genetics,  metabolism*
Grant Support
ID/Acronym/Agency:
AR052646/AR/NIAMS NIH HHS; HL073399/HL/NHLBI NIH HHS; R01 EY022091/EY/NEI NIH HHS; U54 AR052646/AR/NIAMS NIH HHS
Chemical
Reg. No./Substance:
0/Hexim1 protein, mouse; 0/Muscle Proteins; 0/Transcription Factors; EC 2.7.11.-/Positive Transcriptional Elongation Factor B
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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