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Lookup NU author(s): Professor Jordi Diaz ManeraORCiD
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© 2018 The Author(s). Duchenne muscle dystrophy (DMD) is a genetic disorder characterized by progressive skeletal muscle weakness. Dystrophin deficiency induces instability of the sarcolemma during muscle contraction that leads to muscle necrosis and replacement of muscle by fibro-adipose tissue. Several therapies have been developed to counteract the fibrotic process. We report the effects of nintedanib, a tyrosine kinase inhibitor, in the mdx murine model of DMD. Nintedanib reduced proliferation and migration of human fibroblasts in vitro and decreased the expression of fibrotic genes such as COL1A1, COL3A1, FN1, TGFB1, and PDGFA. We treated seven mdx mice with 60 mg/kg/day nintedanib for 1 month. Electrophysiological studies showed an increase in the amplitude of the motor action potentials and an improvement of the morphology of motor unit potentials in the animals treated. Histological studies demonstrated a significant reduction of the fibrotic areas present in the skeletal muscles. Analysis of mRNA expression from muscles of treated mice showed a reduction in Col1a1, Col3a1, Tgfb1, and Pdgfa. Western blot showed a reduction in the expression of collagen I in skeletal muscles. In conclusion, nintedanib reduced the fibrotic process in a murine model of dystrophinopathy after 1 month of treatment, suggesting its potential use as a therapeutic drug in DMD patients.
Author(s): Pinol-Jurado P, Suarez-Calvet X, Fernandez-Simon E, Gallardo E, de la Oliva N, Martinez-Muriana A, Gomez-Galvez P, Escudero LM, Perez-Peiro M, Wollin L, de Luna N, Navarro X, Illa I, Diaz-Manera J
Publication type: Article
Publication status: Published
Journal: Cell Death and Disease
Online publication date: 10/07/2018
Acceptance date: 14/06/2018
Date deposited: 25/02/2020
ISSN (electronic): 2041-4889
Publisher: Nature Publishing Group
PubMed id: 29991677
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