Prevention of muscle fibrosis and myonecrosis in mdx mice by suramin, a TGF-β1 blocker.
Fibrosis is a pathological feature observed in patients with Duchenne muscular dystrophy (DMD) and in mdx mice, the experimental model of DMD. We evaluated the effect of suramin, a transforming growth factor-beta 1 (TGF-β1) blocker, on fibrosis in mdx mice. mdx mice (6 months old) received suramin for 7 weeks. Suramin- and saline-treated (control) mdx mice performed exercise on a treadmill to worsen disease progression. Immunoblotting showed an increase of TGF-β1 in mdx diaphragm, limb, and cardiac muscles. Suramin decreased creatine kinase in mdx mice and attenuated fibrosis in all muscles studied, except for cardiac muscle. Suramin protected limb muscles against damage and reduced the exercise-induced loss of strength over time. These findings support a role for TGF-β1 in fibrinogenesis and myonecrosis during the later stages of disease in mdx mice. Suramin might be a useful therapeutic alternative for the treatment of dystrophinopathies.
Departamento de Anatomia, Biologia Celular, Fisiologia e Biofísica, Instituto de Biologia, Universidade Estadual de Campinas, Campinas, SãoPaulo 13083-970, Brazil.
Ana Paula Tiemi
AP
Taniguti
Adriana
A
Pertille
Cíntia Yuri
CY
Matsumura
Humberto
H
Santo Neto
Maria Julia
MJ
Marques
D000818:Animals; D003402:Creatine Kinase / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D005355:Fibrosis; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018101:Mice, Inbred mdx; D018485:Muscle Fibers, Skeletal / Q000473:pathology*; D018482:Muscle, Skeletal / Q000473:pathology*; D009336:Necrosis; D010805:Physical Conditioning, Animal / Q000009:adverse effects; D013498:Suramin / Q000494:pharmacology* / Q000627:therapeutic use; D053773:Transforming Growth Factor beta1 / Q000037:antagonists & inhibitors* / Q000502:physiology
D053773:Transforming Growth Factor beta1; D013498:Suramin; D003402:Creatine Kinase