Please use this identifier to cite or link to this item: https://doi.org/10.1242/jcs.136648
Title: Sharp-1 regulates TGF-β signaling and skeletal muscle regeneration
Authors: Acharjee, S.
Chung, T.-K. 
Gopinadhan, S.
Shankar, S.R. 
Wang, Y.
Li, L.
Vercherat, C.
Gulbagci, N.T.
Rossner, M.
Taneja, R. 
Keywords: Degeneration
Fibrosis
Myofibroblast
Regeneration
Skeletal muscle
TGF-β
Issue Date: 1-Feb-2014
Publisher: Company of Biologists
Citation: Acharjee, S., Chung, T.-K., Gopinadhan, S., Shankar, S.R., Wang, Y., Li, L., Vercherat, C., Gulbagci, N.T., Rossner, M., Taneja, R. (2014-02-01). Sharp-1 regulates TGF-β signaling and skeletal muscle regeneration. Journal of Cell Science 127 (3) : 599-608. ScholarBank@NUS Repository. https://doi.org/10.1242/jcs.136648
Rights: Attribution 4.0 International
Abstract: Sharp-1 is a basic helix-loop-helix (bHLH) transcriptional repressor that is involved in a number of cellular processes. Our previous studies have demonstrated that Sharp-1 is a negative regulator of skeletal myogenesis and it blocks differentiation of muscle precursor cells by modulating the activity of MyoD. In order to understand its role in pre-and post-natal myogenesis, we assessed skeletal muscle development and freeze-injury-induced regeneration in Sharp-1-deficient mice. We show that embryonic skeletal muscle development is not impaired in the absence of Sharp-1; however, post-natally, the regenerative capacity is compromised. Although the initial phases of injury-induced regeneration proceed normally in Sharp-1-/- mice, during late stages, the mutant muscle exhibits necrotic fibers, calcium deposits and fibrosis. TGF-β expression, as well as levels of phosphorylated Smad2 and Smad3, are sustained in the mutant tissue and treatment with decorin, which blocks TGF-β signaling, improves the histopathology of Sharp-1-/- injured muscles. In vitro, Sharp-1 associates with Smad3, and its overexpression inhibits TGF-β-and Smad3-mediated expression of extracellular matrix genes in myofibroblasts. These results demonstrate that Sharp-1 regulates muscle regenerative capacity, at least in part, by modulation of TGF-β signaling. © 2014. Published by The Company of Biologists Ltd.
Source Title: Journal of Cell Science
URI: http://scholarbank.nus.edu.sg/handle/10635/125671
ISSN: 00219533
DOI: 10.1242/jcs.136648
Rights: Attribution 4.0 International
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