INTRODUCTION: Duchenne Muscular Dystrophy (DMD) is characterized by the lack of dystrophin that leads to severe myofiber degeneration. We have shown that endomysial fibrosis is correlated with age at ambulation loss in DMD patients. However, the dystrophin-deficient mdx mouse does not have fibrotic lesions in adult limb muscles. Here, we describe a model of chronic mechanical muscle injury that triggers chronic lesions in mdx hindlimb muscle. METHODS: Micromechanical injuries were performed daily in tibialis anterior muscles for 2 weeks. RESULTS: Endomysial fibrosis appeared beginning 1 week post-injury, remained stable for 3 months and was associated with loss of specific maximal force. Fibrosis was associated with an increased expression of factors involved in fibrogenesis including α-smooth muscle actin, connective tissue growth factor, and lysyl oxidase, which colocalized with collagen deposits. CONCLUSIONS: This induced fibrotic dystrophic model may be useful to study mechanisms of fibrosis in dystrophinopathies and to evaluate antifibrotic treatments.
INTRODUCTION:Duchenne Muscular Dystrophy (DMD) is characterized by the lack of dystrophin that leads to severe myofiber degeneration. We have shown that endomysial fibrosis is correlated with age at ambulation loss in DMDpatients. However, the dystrophin-deficient mdx mouse does not have fibrotic lesions in adult limb muscles. Here, we describe a model of chronic mechanical muscle injury that triggers chronic lesions in mdx hindlimb muscle. METHODS: Micromechanical injuries were performed daily in tibialis anterior muscles for 2 weeks. RESULTS: Endomysial fibrosis appeared beginning 1 week post-injury, remained stable for 3 months and was associated with loss of specific maximal force. Fibrosis was associated with an increased expression of factors involved in fibrogenesis including α-smooth muscle actin, connective tissue growth factor, and lysyl oxidase, which colocalized with collagen deposits. CONCLUSIONS: This induced fibrotic dystrophic model may be useful to study mechanisms of fibrosis in dystrophinopathies and to evaluate antifibrotic treatments.
Authors: Jia Li; Maureen Fredericks; Marishka Cannell; Kathryn Wang; Dianne Sako; Michelle C Maguire; Rosa Grenha; Katia Liharska; Lavanya Krishnan; Troy Bloom; Elitza P Belcheva; Pedro A Martinez; Roselyne Castonguay; Sarah Keates; Mark J Alexander; Hyunwoo Choi; Asya V Grinberg; R Scott Pearsall; Paul Oh; Ravindra Kumar; Rajasekhar Nvs Suragani Journal: J Clin Invest Date: 2021-02-15 Impact factor: 14.808
Authors: Dario R Lemos; Farshad Babaeijandaghi; Marcela Low; Chih-Kai Chang; Sunny T Lee; Daniela Fiore; Regan-Heng Zhang; Anuradha Natarajan; Sergei A Nedospasov; Fabio M V Rossi Journal: Nat Med Date: 2015-06-08 Impact factor: 53.440
Authors: Moa Fransson; Johan Brännström; Ida Duprez; Magnus Essand; Katarina Le Blanc; Olle Korsgren; Peetra U Magnusson Journal: Regen Med Res Date: 2015-09-30