Gamma interferon as an antifibrosis agent in skeletal muscle.

Abstract

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.

• Authors: William Foster, Yong Li, Arvydas Usas, George Somogyi, Johnny Huard
• Journal: Journal of orthopaedic research : official publication of the Orthopaedic Research Society (J Orthop Res) Vol. 21 Issue 5 Pg. 798-804 (Sep 2003) ISSN: 0736-0266 [Print] United States
• PMID: 12919866 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Tgfb1 protein, mouse
• Transforming Growth Factor beta
• Transforming Growth Factor beta1
• Interferon-gamma

Topics

• Animals
• Cells, Cultured
• Dose-Response Relationship, Drug
• Down-Regulation
• Fibroblasts (drug effects)
• Fibrosis
• Injections, Intramuscular
• Interferon-gamma (administration & dosage, pharmacology)
• Lacerations (pathology, physiopathology)
• Mice
• Mice, Inbred C57BL
• Muscle Contraction (drug effects)
• Muscle, Skeletal (drug effects, injuries, pathology)
• Myoblasts (drug effects, metabolism)
• Regeneration (drug effects)
• Transforming Growth Factor beta (antagonists & inhibitors)
• Transforming Growth Factor beta1
• Wound Healing (drug effects)