title: HEXIM1 controls satellite cell expansion after injury to regulate skeletal muscle regeneration.
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 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.affiliation: Department of Cell Biology, State University of New York Downstate Medical Center,New York, New York, USA.
authors.forename: Peng
authors.initials: P
authors.lastname: Hong
authors.forename: Kang
authors.initials: K
authors.lastname: Chen
authors.forename: Bihui
authors.initials: B
authors.lastname: Huang
authors.forename: Min
authors.initials: M
authors.lastname: Liu
authors.forename: Miao
authors.initials: M
authors.lastname: Cui
authors.forename: Inna
authors.initials: I
authors.lastname: Rozenberg
authors.forename: Brahim
authors.initials: B
authors.lastname: Chaqour
authors.forename: Xiaoyue
authors.initials: X
authors.lastname: Pan
authors.forename: Elisabeth R
authors.initials: ER
authors.lastname: Barton
authors.forename: Xian-Cheng
authors.initials: XC
authors.lastname: Jiang
authors.forename: M A Q
authors.initials: MA
authors.lastname: Siddiqui
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000502:physiology*; D049109:Cell Proliferation; D051379:Mice; D008817:Mice, Mutant Strains; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000293:injuries* / Q000378:metabolism*; D042925:Positive Transcriptional Elongation Factor B / Q000378:metabolism; D016601:RNA-Binding Proteins; D012038:Regeneration / Q000502:physiology*; D032496:Satellite Cells, Skeletal Muscle / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: C118642:Hexim1 protein, mouse; D009124:Muscle Proteins; D016601:RNA-Binding Proteins; D014157:Transcription Factors; D042925:Positive Transcriptional Elongation Factor B