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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 |
Appears in Collections: | Staff Publications Elements |
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