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Antifibrotic effects of suramin in injured skeletal muscle after laceration

¹Department of Orthopaedic Surgery, Growth and Development Laboratory, Children's Hospital of Pittsburgh and University of Pittsburgh, ²Department of Orthopaedic Surgery, Division of Sports Medicine, Musculoskeletal Research Center, University of Pittsburgh, ⁴Departments of Pharmacology and ⁵Molecular Genetics and Biochemistry, University of Pittsburgh, Pittsburgh, Pennsylvania 15213; and ³Department of Orthopaedic Surgery, Chang Gung Memorial Hospital, Kueishan, Taoyuan, Taiwan

Submitted 4 October 2002 ; accepted in final form 27 April 2003

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)-₁ 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 µg/ml) can effectively decrease fibroblast proliferation and fibrotic-protein expression (-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.

muscle injury; fibrosis; transforming growth factor-₁; suramin; muscle regeneration

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