Premium
A comparison of factors associated with collagen metabolism in different skeletal muscles from dystrophic ( mdx ) mice: Impact of pirfenidone
Author(s) -
Gosselin Luc E.,
Williams Jacqueline E.,
Personius Kirkwood,
Farkas Gaspar A.
Publication year - 2007
Publication title -
muscle and nerve
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.025
H-Index - 145
eISSN - 1097-4598
pISSN - 0148-639X
DOI - 10.1002/mus.20681
Subject(s) - pirfenidone , hydroxyproline , endocrinology , medicine , skeletal muscle , fibrosis , genioglossus , muscular dystrophy , extracellular matrix , chemistry , idiopathic pulmonary fibrosis , biochemistry , lung , obstructive sleep apnea
Skeletal muscles in mdx mice exhibit differential degrees of pathological changes and fibrosis. The purpose of this study was to examine differences in various indices of collagen metabolism in skeletal muscles with widely different functions and activity profiles in mdx mice, and to determine whether pirfenidone would attenuate the development of fibrosis. Mice in the pirfenidone group were orally fed pirfenidone (500 mg/kg) daily for 4 weeks. Marked differences were noted in hydroxyproline concentration between muscles, which could not be explained solely by the level of type I collagen and transforming growth factor‐β1 (TGF‐β1) mRNA. In normal mice, matrix metalloproteinase (MMP)‐2 mRNA was significantly higher in the gastrocnemius than in the diaphragm or genioglossus muscles, suggesting that collagen degradation plays an important role in regulating collagen accretion in skeletal muscle. In mdx mice, the levels of both MMP‐2 and MMP‐9 mRNA were significantly elevated relative to control, although the response was muscle specific. Pirfenidone treatment resulted in a significant reduction in the level of hydroxyproline concentration across all muscles, although the effect was small. Results from this study reveal intrinsic dissimilarities in collagen metabolism between functionally different skeletal muscles. Moreover, the pharmacological use of pirfenidone may be beneficial in preventing fibrosis in muscular dystrophy. Muscle Nerve, 2006