Gamma interferon as an antifibrosis agent in skeletal muscle.
Muscle injuries are a common problem in sports medicine. Skeletal muscle can regenerate itself, but the process is both slow and incomplete. Previously we and others have used growth factors to improve the regeneration of muscle, but the muscle healing was impeded by scar tissue formation. However, when we blocked the fibrosis process with decorin, an antifibrosis agent, we improved the muscle healing. Here we show that gammainterferon (gammaINF)--a cytokine that inhibits the signaling of transforming growth factor beta1 (TGFbeta1), a fibrotic stimulator--reduces fibrosis formation and improves the healing of lacerated skeletal muscle. With gammaINF treatment, the growth rate of muscle-derived fibroblasts was reduced and the level of fibrotic protein expression induced by TGFbeta1 (including TGFbeta1, vimentin, and alpha-smooth muscle actin) was down-regulated in vitro. In a mouse laceration model, the area of fibrosis decreased when gammaINF was injected at either 1 or 2 weeks after injury. More importantly, the injection of gammaINF at either 1 or 2 weeks post-injury was found to improve muscle function in terms of both fast-twitch and tetanic strength. This study demonstrates that gammaINF is a potent antifibrosis agent that can improve muscle healing after laceration injury.
Foster
William
W
Growth and Development Laboratory, Department of Orthopaedic Surgery, 4151 Rangos Research Center, Children's Hospital of Pittsburgh and University of Pittsburgh, 3705 Fifth Avenue, Pittsburgh, PA 15213-2583, USA.
Li
Yong
Y
Usas
Arvydas
A
Somogyi
George
G
Huard
Johnny
J
D000818:Animals; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D005347:Fibroblasts / Q000187:drug effects; D005355:Fibrosis; D007273:Injections, Intramuscular; D007371:Interferon-gamma / Q000008:administration & dosage / Q000494:pharmacology*; D022125:Lacerations / Q000473:pathology* / Q000503:physiopathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009119:Muscle Contraction / Q000187:drug effects; D018482:Muscle, Skeletal / Q000187:drug effects / Q000293:injuries* / Q000473:pathology; D032446:Myoblasts / Q000187:drug effects / Q000378:metabolism; D012038:Regeneration / Q000187:drug effects; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors; D053773:Transforming Growth Factor beta1; D014945:Wound Healing / Q000187:drug effects*
C508961:Tgfb1 protein, mouse; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D007371:Interferon-gamma