title: Intermittent stretching induces fibrosis in denervated rat muscle.
abstract: BACKGROUND
  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.
authors.affiliation: Research Laboratory of Neurological Physiotherapy, Department of Physiotherapy, Federal University of São Carlos, São Carlos, São Paulo, Brazil.
authors.forename: Fernanda M
authors.initials: FM
authors.lastname: Faturi
authors.affiliation: Research Laboratory of Neurological Physiotherapy, Department of Physiotherapy, Federal University of São Carlos, São Carlos, São Paulo, Brazil.
authors.forename: Rúbia C
authors.initials: RC
authors.lastname: Franco
authors.affiliation: Research Laboratory of Neurological Physiotherapy, Department of Physiotherapy, Federal University of São Carlos, São Carlos, São Paulo, Brazil.
authors.forename: Davilene
authors.initials: D
authors.lastname: Gigo-Benato
authors.affiliation: Research Laboratory of Neurological Physiotherapy, Department of Physiotherapy, Federal University of São Carlos, São Carlos, São Paulo, Brazil.
authors.forename: Andriette C
authors.initials: AC
authors.lastname: Turi
authors.affiliation: Research Laboratory of Neurological Physiotherapy, Department of Physiotherapy, Federal University of São Carlos, São Carlos, São Paulo, Brazil.
authors.forename: Marcela A
authors.initials: MA
authors.lastname: Silva-Couto
authors.affiliation: Laboratory of Muscle Plasticity, Department of Physiotherapy, Federal University of São Carlos, São Carlos, São Paulo, Brazil.
authors.forename: Sabrina P
authors.initials: SP
authors.lastname: Messa
authors.affiliation: Research Laboratory of Neurological Physiotherapy, Department of Physiotherapy, Federal University of São Carlos, São Carlos, São Paulo, Brazil.
authors.forename: Thiago L
authors.initials: TL
authors.lastname: Russo
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D020782:Matrix Metalloproteinases / Q000235:genetics / Q000378:metabolism; D009121:Muscle Denervation; D018485:Muscle Fibers, Skeletal / Q000473:pathology*; D052580:Muscle Stretching Exercises / Q000009:adverse effects*; D009133:Muscular Atrophy / Q000473:pathology* / Q000503:physiopathology*; D055435:Myostatin / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger; D051381:Rats; D012518:Sarcomeres / Q000473:pathology; D018709:Statistics, Nonparametric; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism
chemical_list: D055435:Myostatin; D012333:RNA, Messenger; C576839:TIMP1 protein, rat; D019715:Tissue Inhibitor of Metalloproteinase-1; D053773:Transforming Growth Factor beta1; D020782:Matrix Metalloproteinases
keywords: muscle atrophy; neurorehabilitation; physiotherapy; skeletal muscle; stretching