Sca-1 expression is required for efficient remodeling of the extracellular matrix during skeletal muscle regeneration |
| |
Authors: | Kimberly A. Kafadar Yusra Ahmad Fabio Rossi |
| |
Affiliation: | a Emory University, Department of Pharmacology, Atlanta, GA 30322, USA b University of British Columbia, The Biomedical Research Centre, Vancouver, BC, Canada V6T 1Z3 |
| |
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. |
| |
Keywords: | Skeletal muscle Sca-1 Regeneration Satellite cell MMP Extracellular matrix Fibrosis Stem cells |
本文献已被 ScienceDirect 等数据库收录! |
|