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Author Notes:

Address correspondence to: Grace K. Pavlath, Emory University, Atlanta, GA 30322, Email: gpavlat@emory.edu, Phone: 404-727-3353, Fax: 404-727-0365

We thank William Stanford and Mortaza Bonyadi for generously providing Sca-1-/- mice and for helpful discussions, Todd Mills for help generating mdxSca-1-/- mice, and Karen Kafadar for assistance with statistical analysis.

Subjects:

Research Funding:

This work was supported by National Institutes of Health (NIH) grant AR051372 (G.K.P.), NRSA Fellowship AR052267-01 and a Frederick Garner Cottrell Postdoctoral Enhancement Award, (K.A.K.), Canadian Institute of Health Research (CIHR) grant MOP-82864 and a grant from the Jesse's Journey Foundation (F.M.V.R.), NSERC (PGSD2-362406-2008) and a Michael Smith Foundation of Health Research predoctoral fellowship (ST-JGS-062(06-1)BM) (L.S.).

Keywords:

  • skeletal muscle
  • Sca-1
  • regeneration
  • satellite cell
  • MMP
  • extracellular matrix
  • fibrosis
  • stem cells

Sca-1 expression is required for efficient remodeling of the extracellular matrix during skeletal muscle regeneration

Tools:

Journal Title:

Developmental Biology

Volume:

Volume 326, Number 1

Publisher:

, Pages 47-59

Type of Work:

Article | Post-print: After Peer Review

Abstract:

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.

Copyright information:

© 2009 Elsevier

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