Conditional expression of TGF-β1 in skeletal muscles causes endomysial fibrosis and myofibers atrophy

Jigna Narola, Sachchida Nand Pandey, Adam Bleier Glick, Yi Wen Chen

Research output: Contribution to journalArticle

22 Citations (Scopus)

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-β1 transgenic 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.

Original languageEnglish (US)
Article numbere79356
JournalPloS one
Volume8
Issue number11
DOIs
StatePublished - Nov 14 2013

Fingerprint

atrophy
fibrosis
Atrophy
Muscle
skeletal muscle
Skeletal Muscle
Fibrosis
Muscle Weakness
Muscles
muscles
Phenotype
mice
Muscular Atrophy
Doxycycline
Transgenes
Transforming Growth Factor beta
Transgenic Mice
Regeneration
transforming growth factor beta 1
Up-Regulation

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

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title = "Conditional expression of TGF-β1 in skeletal muscles causes endomysial fibrosis and myofibers atrophy",
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-β1 transgenic 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.",
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Conditional expression of TGF-β1 in skeletal muscles causes endomysial fibrosis and myofibers atrophy. / Narola, Jigna; Pandey, Sachchida Nand; Glick, Adam Bleier; Chen, Yi Wen.

In: PloS one, Vol. 8, No. 11, e79356, 14.11.2013.

Research output: Contribution to journalArticle

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