title: Upregulation of transforming growth factor-β signaling in a rat model of rotator cuff tears.
abstract: BACKGROUND
  Muscle atrophy, fatty infiltration, and fibrosis of the muscle have been described as important factors governing outcome after rotator cuff injury and repair. Muscle fibrosis is also thought to have a role in determining muscle compliance at the time of surgery. The transforming growth factor-β (TGF-β) pathways are highly conserved pathways that exert a potent level of control over muscle gene expression and are critical regulators of fibrosis in multiple organ systems. It has been shown that TGF-β can regulate important pathways of muscle atrophy, including the Akt/mammalian target of rapamycin pathway. The purpose of this study was to evaluate the expression of TGF-β and its downstream effectors of fibrosis after a massive rotator cuff tear (RCT) in a previously established rat model.
  
  
  METHODS
  To simulate a massive RCT, infraspinatus and supraspinatus tenotomy and suprascapular nerve transection were performed on Sprague-Dawley rats with use of a validated model. Two and 6 weeks after surgery, supraspinatus muscles were harvested to study alterations in TGF-β signaling by Western blotting, quantitative polymerase chain reaction, and histologic analysis.
  
  
  RESULTS
  There was a significant increase in fibrosis in the rotator cuff muscle after RCT in our animal model. There was a concomitant increase in TGF-β gene and protein expression at both 2 and 6 weeks after RCT. Evaluation of the TGF-β signaling pathway revealed an increase in SMAD2 activation but not in SMAD3. There was an increase in profibrotic markers collagen I, collagen III, and α-smooth muscle actin.
  
  
  CONCLUSIONS
  TGF-β signaling is significantly upregulated in rat supraspinatus muscles after RCTs.
authors.affiliation: Department of Veterans Affairs, San Francisco Veterans Affairs Medical Center, San Francisco, CA, USA; Department of Orthopaedic Surgery, University of California, San Francisco, CA, USA.
authors.forename: Xuhui
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Veterans Affairs, San Francisco Veterans Affairs Medical Center, San Francisco, CA, USA; Department of Orthopaedic Surgery, University of California, San Francisco, CA, USA.
authors.forename: Sunil K
authors.initials: SK
authors.lastname: Joshi
authors.affiliation: Department of Veterans Affairs, San Francisco Veterans Affairs Medical Center, San Francisco, CA, USA; Department of Orthopaedic Surgery, University of California, San Francisco, CA, USA.
authors.forename: Bharat
authors.initials: B
authors.lastname: Ravishankar
authors.affiliation: Department of Orthopaedic Surgery, University of California, San Francisco, CA, USA.
authors.forename: Dominique
authors.initials: D
authors.lastname: Laron
authors.affiliation: Department of Veterans Affairs, San Francisco Veterans Affairs Medical Center, San Francisco, CA, USA; Department of Orthopaedic Surgery, University of California, San Francisco, CA, USA.
authors.forename: Hubert T
authors.initials: HT
authors.lastname: Kim
authors.affiliation: Department of Orthopaedic Surgery, University of California, San Francisco, CA, USA. Electronic address: feeleyb@orthosurg.ucsf.edu.
authors.forename: Brian T
authors.initials: BT
authors.lastname: Feeley
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D005355:Fibrosis / Q000378:metabolism; D059348:Peripheral Nerve Injuries / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D017006:Rotator Cuff / Q000378:metabolism*; D000070636:Rotator Cuff Injuries; D013708:Tendon Injuries / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000096:biosynthesis*; D015854:Up-Regulation
chemical_list: D012333:RNA, Messenger; D016212:Transforming Growth Factor beta
keywords: Massive rotator cuff tear; fibrosis; transforming growth factor-β