| First Author | Narola J | Year | 2013 |
| Journal | PLoS One | Volume | 8 |
| Issue | 11 | Pages | e79356 |
| PubMed ID | 24244485 | Mgi Jnum | J:209702 |
| Mgi Id | MGI:5568329 | Doi | 10.1371/journal.pone.0079356 |
| Citation | Narola J, et al. (2013) Conditional expression of TGF-beta1 in skeletal muscles causes endomysial fibrosis and myofibers atrophy. PLoS One 8(11):e79356 |
| abstractText | To study the effects of transforming growth factor beta 1 (TGF-beta1) on fibrosis and failure of regeneration of skeletal muscles, we generated a tet-repressible muscle-specific TGF-beta1 transgenic mouse in which expression of TGF-beta1 is controlled by oral doxycycline. The mice developed muscle weakness and atrophy after TGF-beta1 over-expression. We defined the group of mice that showed phenotype within 2 weeks as early onset (EO) and the rest as late onset (LO), which allowed us to further examine phenotypic differences between the groups. While only mice in the EO group showed significant muscle weakness, pathological changes including endomysial fibrosis and smaller myofibers were observed in both groups at two weeks after the TGF-beta1 was over-expressed. In addition, the size of the myofibers and collagen accumulation were significantly different between the two groups. The amount of latent and active TGF-beta1 in the muscle and circulation were significantly higher in the EO group compared to the LO or control groups. The up-regulation of the latent TGF-beta1 indicated that endogenous TGF-beta1 was induced by the expression of the TGF-beta1 transgene. Our studies showed that the primary effects of TGF-beta1 over-expression in skeletal muscles are muscle wasting and endomysial fibrosis. In addition, the severity of the pathology is associated with the total amount of TGF-beta1 and the expression of endogenous TGF-beta1. The findings suggest that an auto-feedback loop of TGF-beta1 may contribute to the severity of phenotypes. |
