title: Sca-1 is negatively regulated by TGF-beta1 in myogenic cells.
abstract: Sca-1 (stem cell antigen-1) is a member of the Ly-6 family of proteins and regulates cell proliferation, differentiation, and self-renewal in multiple tissues. In skeletal muscle, Sca-1 inhibits both proliferation and differentiation of myogenic cells. Sca-1 expression is dynamically regulated during muscle regeneration, and mice lacking Sca-1 display increased fibrosis following muscle injury. Here, we show that Sca-1 expression is negatively regulated by TGF-β1 and that this inhibition is dependent on Smad3. We demonstrate that levels of TGF-β1 in skeletal muscle rapidly increase on injury and that the majority of this TGFβ1 is produced by infiltrating macrophages. Sca-1 is expressed in multiple cell types, and we demonstrate that TGF-β1 represses Sca-1 expression in T cells and other immune cell populations derived from the spleen, indicating that regulation by TGF-β1 is a general feature of Sca-1 expression in multiple cell types. Elucidation of the mechanisms by which Sca-1 expression is regulated may aid in the understanding of muscle homeostasis, potentially identifying novel therapeutic targets for muscle diseases.
authors.affiliation: Department of Infectious Diseases, Boston Medical Center, Boston, Massachusetts, USA.
authors.forename: Kimberly K
authors.initials: KK
authors.lastname: Long
authors.forename: Monty
authors.initials: M
authors.lastname: Montano
authors.forename: Grace K
authors.initials: GK
authors.lastname: Pavlath
mesh_terms: D000818:Animals; D000950:Antigens, Ly / Q000096:biosynthesis*; D008565:Membrane Proteins / Q000096:biosynthesis*; D051379:Mice; D008810:Mice, Inbred C57BL; D018482:Muscle, Skeletal / Q000502:physiology*; D032448:Myoblasts, Skeletal / Q000502:physiology*; D012038:Regeneration / Q000502:physiology*; D015398:Signal Transduction; D051900:Smad3 Protein / Q000502:physiology; D053773:Transforming Growth Factor beta1 / Q000502:physiology*
chemical_list: D000950:Antigens, Ly; C074650:Ly6a protein, mouse; D008565:Membrane Proteins; D051900:Smad3 Protein; C497791:Smad3 protein, mouse; D053773:Transforming Growth Factor beta1