Sca-1 expression is required for efficient remodeling of the extracellular matrix during skeletal muscle regeneration.
Sca-1 (Stem Cell Antigen-1) is a member of the Ly-6 family proteins that functions in cell growth, differentiation, and self-renewal in multiple tissues. In skeletal muscle Sca-1 negatively regulates myoblast proliferation and differentiation, and may function in the maintenance of progenitor cells. We investigated the role of Sca-1 in skeletal muscle regeneration and show here that Sca-1 expression is upregulated in a subset of myogenic cells upon muscle injury. We demonstrate that extract from crushed muscle upregulates Sca-1 expression in myoblasts in vitro, and that this effect is reversible and independent of cell proliferation. Sca-1(-/-) mice exhibit defects in muscle regeneration, with the development of fibrosis following injury. Sca-1(-/-) muscle displays reduced activity of matrix metalloproteinases, critical regulators of extracellular matrix remodeling. Interestingly, we show that the number of satellite cells is similar in wild-type and Sca-1(-/-) muscle, suggesting that in satellite cells Sca-1 does not play a role in self-renewal. We hypothesize that Sca-1 upregulates, directly or indirectly, the activity of matrix metalloproteinases, leading to matrix breakdown and efficient muscle regeneration. Further elucidation of the role of Sca-1 in matrix remodeling may aid in the development of novel therapeutic strategies for the treatment of fibrotic diseases.
Kafadar
Kimberly A
KA
Emory University, Department of Pharmacology, Atlanta, GA 30322, USA.
Yi
Lin
L
Ahmad
Yusra
Y
So
Leslie
L
Rossi
Fabio
F
Pavlath
Grace K
GK
D000818:Animals; D000950:Antigens, Ly / Q000502:physiology*; D049109:Cell Proliferation; D002478:Cells, Cultured; D005109:Extracellular Matrix / Q000378:metabolism*; D020782:Matrix Metalloproteinases / Q000378:metabolism; D008565:Membrane Proteins / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D018482:Muscle, Skeletal / Q000502:physiology*; D032446:Myoblasts / Q000502:physiology*; D012038:Regeneration / Q000502:physiology*; D015854:Up-Regulation / Q000502:physiology
D000950:Antigens, Ly; C074650:Ly6a protein, mouse; D008565:Membrane Proteins; D020782:Matrix Metalloproteinases