Document Type
Journal Article
Publication Date
11-14-2013
Journal
PLoS ONE
Volume
Volume 8, Issue 11
Inclusive Pages
Article number e79356
Keywords
Gene Expression; Muscle, Skeletal--metabolism; Muscle, Skeletal--pathology; Muscular Atrophy--genetics; Muscular Atrophy--pathology; Transforming Growth Factor beta1--genetics
Abstract
To study the effects of transforming growth factor beta 1 (TGF-β1) on fibrosis and failure of regeneration of skeletal muscles, we generated a tet-repressible muscle-specific TGF-β1transgenic mouse in which expression of TGF-β1 is controlled by oral doxycycline. The mice developed muscle weakness and atrophy after TGF-β1 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-β1 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-β1 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-β1 indicated that endogenous TGF-β1 was induced by the expression of the TGF-β1 transgene. Our studies showed that the primary effects of TGF-β1 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-β1 and the expression of endogenous TGF-β1. The findings suggest that an auto-feedback loop of TGF-β1 may contribute to the severity of phenotypes.
Creative Commons License
This work is licensed under a Creative Commons Attribution 3.0 License.
APA Citation
Narola, J., Pandey, S.N., Glick, A., Chen, Y. (2013). Conditional expression of TGF-β1 in skeletal muscles causes endomysial fibrosis and myofibers atrophy. PLoS ONE, 8(11):e79356.
Peer Reviewed
1
Open Access
1
Comments
Reproduced with permission of PLoS ONE.