title: Bowman-Birk inhibitor attenuates dystrophic pathology in mdx mice.
abstract: Bowman-Birk inhibitor concentrate (BBIC), a serine protease inhibitor, has been shown to diminish disuse atrophy of skeletal muscle. Duchenne muscular dystrophy (DMD) results from a loss of dystrophin protein and involves an ongoing inflammatory response, with matrix remodeling and activation of transforming growth factor (TGF)-β(1) leading to tissue fibrosis. Inflammatory-mediated increases in extracellular protease activity may drive much of this pathological tissue remodeling. Hence, we evaluated the ability of BBIC, an extracellular serine protease inhibitor, to impact pathology in the mouse model of DMD (mdx mouse). Mdx mice fed 1% BBIC in their diet had increased skeletal muscle mass and tetanic force and improved muscle integrity (less Evans blue dye uptake). Importantly, mdx mice treated with BBIC were less susceptible to contraction-induced injury. Changes consistent with decreased degeneration/regeneration, as well as reduced TGF-β(1) and fibrosis, were observed in the BBIC-treated mdx mice. While Akt signaling was unchanged, myostatin activitation and Smad signaling were reduced. Given that BBIC treatment increases mass and strength, while decreasing fibrosis in skeletal muscles of the mdx mouse, it should be evaluated as a possible therapeutic to slow the progression of disease in human DMD patients.
authors.affiliation: Department of Physiology, School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: C A
authors.initials: CA
authors.lastname: Morris
authors.forename: J T
authors.initials: JT
authors.lastname: Selsby
authors.forename: L D
authors.initials: LD
authors.lastname: Morris
authors.forename: K
authors.initials: K
authors.lastname: Pendrak
authors.forename: H L
authors.initials: HL
authors.lastname: Sweeney
mesh_terms: D000284:Administration, Oral; D000818:Animals; D004195:Disease Models, Animal; D018450:Disease Progression; D005355:Fibrosis; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018101:Mice, Inbred mdx; D009119:Muscle Contraction / Q000187:drug effects; D053580:Muscle Strength / Q000187:drug effects; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D020388:Muscular Dystrophy, Duchenne / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D055435:Myostatin / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D051785:Smad Proteins / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D014358:Trypsin Inhibitor, Bowman-Birk Soybean / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: C525912:Mstn protein, mouse; D055435:Myostatin; D051785:Smad Proteins; C508961:Tgfb1 protein, mouse; D053773:Transforming Growth Factor beta1; D014358:Trypsin Inhibitor, Bowman-Birk Soybean; D051057:Proto-Oncogene Proteins c-akt