Antifibrotic effects of suramin in injured skeletal muscle after laceration.
Muscle injuries are very common in traumatology and sports medicine. Although muscle tissue can regenerate postinjury, the healing process is slow and often incomplete; complete recovery after skeletal muscle injury is hindered by fibrosis. Our studies have shown that decreased fibrosis could improve muscle healing. Suramin has been found to inhibit transforming growth factor (TGF)-beta1 expression by competitively binding to the growth factor receptor. We conducted a series of tests to determine the antifibrotic effects of suramin on muscle laceration injuries. Our results demonstrate that suramin (50 microg/ml) can effectively decrease fibroblast proliferation and fibrotic-protein expression (alpha-smooth muscle actin) in vitro. In vivo, direct injection of suramin (2.5 mg) into injured murine muscle resulted in effective inhibition of muscle fibrosis and enhanced muscle regeneration, which led to efficient functional muscle recovery. These results support our hypothesis that prevention of fibrosis could enhance muscle regeneration, thereby facilitating more efficient muscle healing. This study could significantly contribute to the development of strategies to promote efficient muscle healing and functional recovery.
Department of Orthopaedic Surgery, Children's Hospital of Pittsburgh, University of Pittsburgh, Pittsburgh, PA 15213-2583, USA.
Yi-Sheng
YS
Chan
Yong
Y
Li
William
W
Foster
Takashi
T
Horaguchi
George
G
Somogyi
Freddie H
FH
Fu
Johnny
J
Huard
D016475:3T3 Cells; D000199:Actins / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D005347:Fibroblasts / Q000187:drug effects; D005355:Fibrosis; D007267:Injections; D007425:Intracellular Membranes / Q000378:metabolism; 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* / Q000503:physiopathology; D009130:Muscle, Smooth / Q000378:metabolism; D012038:Regeneration / Q000187:drug effects; D013498:Suramin / Q000008:administration & dosage / Q000494:pharmacology*; D014746:Vimentin / Q000378:metabolism; D014945:Wound Healing / Q000187:drug effects
D000199:Actins; D014746:Vimentin; D013498:Suramin