RT Journal Article
T1 Nintedanib decreases muscle fibrosis and improves muscle function in a murine model of dystrophinopathy.
A1 Piñol-Jurado, Patricia
A1 Suárez-Calvet, Xavier
A1 Fernández-Simón, Esther
A1 Gallardo, Eduard
A1 de la Oliva, Natalia
A1 Martínez-Muriana, Anna
A1 Gómez-Gálvez, Pedro
A1 Escudero, Luis M
A1 Pérez-Peiró, María
A1 Wollin, Lutz
A1 de Luna, Noemi
A1 Navarro, Xavier
A1 Illa, Isabel
A1 Díaz-Manera, Jordi
AB 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.
YR 2018
FD 2018-07-10
LK http://hdl.handle.net/10668/12700
UL http://hdl.handle.net/10668/12700
LA en
DS RISalud
RD Apr 6, 2025