Antifibrotic effects of suramin in injured skeletal muscle after laceration

• Published in: Journal of applied physiology (1985) 2003-08, Vol.95 (2), p.771-780
• Main Authors: Chan, Yi-Sheng, Li, Yong, Foster, William, Horaguchi, Takashi, Somogyi, George, Fu, Freddie H, Huard, Johnny
• Format: Article
• Language: English
• Subjects: 3T3 Cells; Actins - metabolism; Animals; Biological and medical sciences; Blotting, Western; Drug therapy; Fibroblasts - drug effects; Fibrosis; Injections; Injuries; Intracellular Membranes - metabolism; Lacerations - pathology; Lacerations - physiopathology; Medical sciences; Mice; Mice, Inbred C57BL; Muscle; Muscle Contraction - drug effects; Muscle, Skeletal - drug effects; Muscle, Skeletal - injuries; Muscle, Skeletal - pathology; Muscle, Skeletal - physiopathology; Muscle, Smooth - metabolism; Muscular system; Pharmacology. Drug treatments; Regeneration - drug effects; Suramin - administration & dosage; Suramin - pharmacology; Vimentin - metabolism; Wound Healing - drug effects
• ISSN: 8750-7587; 1522-1601
• DOI: 10.1152/japplphysiol.00915.2002

1 Department of Orthopaedic Surgery, Growth and Development Laboratory, Children's Hospital of Pittsburgh and University of Pittsburgh, 2 Department of Orthopaedic Surgery, Division of Sports Medicine, Musculoskeletal Research Center, University of Pittsburgh, 4 Departments of Pharmacology and 5 Molecular Genetics and Biochemistry, University of Pittsburgh, Pittsburgh, Pennsylvania 15213; and 3 Department 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 Address for reprint requests and other correspondence: J. Huard, Director, Growth and Development Laboratory, 4151 Rangos Research Center, Children's Hospital of Pittsburgh, 3705 Fifth Ave., Pittsburgh, PA 15213-2583 (E-mail: jhuard+{at}pitt.edu ).