| First Author | Acharjee S | Year | 2014 |
| Journal | J Cell Sci | Volume | 127 |
| Issue | Pt 3 | Pages | 599-608 |
| PubMed ID | 24357723 | Mgi Jnum | J:207514 |
| Mgi Id | MGI:5559010 | Doi | 10.1242/jcs.136648 |
| Citation | Acharjee S, et al. (2014) Sharp-1 regulates TGF-beta signaling and skeletal muscle regeneration. J Cell Sci 127(Pt 3):599-608 |
| abstractText | 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-beta expression, as well as levels of phosphorylated Smad2 and Smad3, are sustained in the mutant tissue and treatment with decorin, which blocks TGF-beta signaling, improves the histopathology of Sharp-1(-/-) injured muscles. In vitro, Sharp-1 associates with Smad3, and its overexpression inhibits TGF-beta- 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-beta signaling. |
