Intermittent stretching induces fibrosis in denervated rat muscle

Muscle Nerve. 2016 Jan;53(1):118-26. doi: 10.1002/mus.24702. Epub 2015 Nov 23.

Abstract

Introduction: Stretching (St) has been used for treating denervated muscles. However, its effectiveness and safety claims require further study.

Methods: Rats were divided into: (1) those with denervated (D) muscles, evaluated 7 or 15 days after sciatic nerve crush injury; (2) those with D muscles submitted to St during 7 or 15 days; and (3) those with normal muscles. Muscle fiber cross-sectional area, serial sarcomere number, sarcomere length, and connective tissue density were measured. MMP-2, MMP-9, TIMP-1, TGF-β1, and myostatin mRNAs were determined by real-time polymerase chain reaction. MMP-2 and MMP-9 activity was evaluated by zymography. Collagen I was localized using immunofluorescence.

Results: St did not prevent muscle atrophy due to denervation, but it increased fibrosis and collagen I deposition at day 15. St also upregulated MMP-9 and TGF-β1 gene expressions at day 7, and myostatin at day 15.

Conclusions: Stretching denervated muscle does not prevent atrophy, but it increases fibrosis via temporal modulation of TGF-β1/myostatin and MMP-9 cascades.

Keywords: muscle atrophy; neurorehabilitation; physiotherapy; skeletal muscle; stretching.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Disease Models, Animal
  • Matrix Metalloproteinases / genetics
  • Matrix Metalloproteinases / metabolism
  • Muscle Denervation*
  • Muscle Fibers, Skeletal / pathology*
  • Muscle Stretching Exercises / adverse effects*
  • Muscular Atrophy / pathology*
  • Muscular Atrophy / physiopathology*
  • Myostatin / genetics
  • Myostatin / metabolism
  • RNA, Messenger
  • Rats
  • Sarcomeres / pathology
  • Statistics, Nonparametric
  • Tissue Inhibitor of Metalloproteinase-1 / genetics
  • Tissue Inhibitor of Metalloproteinase-1 / metabolism
  • Transforming Growth Factor beta1 / genetics
  • Transforming Growth Factor beta1 / metabolism

Substances

  • Myostatin
  • RNA, Messenger
  • TIMP1 protein, rat
  • Tissue Inhibitor of Metalloproteinase-1
  • Transforming Growth Factor beta1
  • Matrix Metalloproteinases