title: The effect of relaxin treatment on skeletal muscle injuries.
abstract: BACKGROUND
  Injured skeletal muscle can repair itself via spontaneous regeneration; however, the overproduction of extracellular matrix and excessive collagen deposition lead to fibrosis. Neutralization of the effect of transforming growth factor-beta 1, a key fibrotic cytokine, on myogenic cell differentiation after muscle injury can prevent fibrosis, enhance muscle regeneration, and thereby improve the functional recovery of injured muscle.
  
  
  OBJECTIVE
  The hormone relaxin, a member of the family of insulin-like growth factors, can act as an antifibrosis agent and improve the healing of injured muscle.
  
  
  METHODS
  Controlled laboratory study.
  
  
  METHODS
  In vitro: Myoblasts (C2C12 cells) and myofibroblasts (transforming growth factor-beta 1-transfected myoblasts) were incubated with relaxin, and cell growth and differentiation were examined. Myogenic and fibrotic protein expression was determined by Western blot analysis. In vivo: Relaxin was injected intramuscularly at different time points after laceration injury. Skeletal muscle healing was evaluated via histologic, immunohistochemical, and physiologic tests.
  
  
  RESULTS
  Relaxin treatment resulted in a dose-dependent decrease in myofibroblast proliferation, down-regulated expression of the fibrotic protein alpha-smooth muscle actin, and promoted the proliferation and differentiation of myoblasts in vitro. Relaxin therapy enhanced muscle regeneration, reduced fibrosis, and improved injured muscle strength in vivo.
  
  
  CONCLUSIONS
  Administration of relaxin can significantly improve skeletal muscle healing.
  
  
  CONCLUSIONS
  These findings may facilitate the development of techniques to eliminate fibrosis, enhance muscle regeneration, and improve functional recovery after muscle injuries.
authors.affiliation: University of Pittsburgh and Children's Hospital of Pittsburgh, PA 15213, USA.
authors.forename: Shinichi
authors.initials: S
authors.lastname: Negishi
authors.forename: Yong
authors.initials: Y
authors.lastname: Li
authors.forename: Arvydas
authors.initials: A
authors.lastname: Usas
authors.forename: Freddie H
authors.initials: FH
authors.lastname: Fu
authors.forename: Johnny
authors.initials: J
authors.lastname: Huard
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D002454:Cell Differentiation; D049109:Cell Proliferation; D003094:Collagen / Q000378:metabolism; D003893:Desmin / Q000378:metabolism; D015536:Down-Regulation; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D005355:Fibrosis; D066298:In Vitro Techniques; D007273:Injections, Intramuscular; D051379:Mice; D018485:Muscle Fibers, Skeletal / Q000378:metabolism; D018482:Muscle, Skeletal / Q000293:injuries* / Q000473:pathology / Q000502:physiology*; D009130:Muscle, Smooth / Q000378:metabolism; D032448:Myoblasts, Skeletal / Q000378:metabolism; D051787:Myogenic Regulatory Factor 5 / Q000378:metabolism; D012038:Regeneration; D012065:Relaxin / Q000494:pharmacology*; D015854:Up-Regulation; D014746:Vimentin / Q000378:metabolism; D014945:Wound Healing / Q000187:drug effects*
chemical_list: D000199:Actins; D003893:Desmin; D051787:Myogenic Regulatory Factor 5; D014746:Vimentin; D012065:Relaxin; D003094:Collagen