No abstract

Despite over 3,000 articles published on dystrophin in the last 15 years, the reasons underlying the progression of the human disease, differential muscle involvement, and disparate phenotypes in different species are not understood. The present experiment employed a screen of 12,488 mRNAs in 16-wk-old mouse mdx muscle at a time when the skeletal muscle is avoiding severe dystrophic pathophysiology, despite the absence of a functional dystrophin protein. A number of transcripts whose levels differed between the mdx and human Duchenne muscular dystrophy were noted. A fourfold decrease in myostatin mRNA in the mdx muscle was noted. Differential upregulation of actin-related protein 2/3 (subunit 4), beta-thymosin, calponin, mast cell chymase, and guanidinoacetate methyltransferase mRNA in the more benign mdx was also observed. Transcripts for oxidative and glycolytic enzymes in mdx muscle were not downregulated. These discrepancies could provide candidates for salvage pathways that maintain skeletal muscle integrity in the absence of a functional dystrophin protein in mdx skeletal muscle.

The purpose of this study was to assess the impact of prednisone treatment for 8 weeks on the level of transforming growth factor-beta 1 (TGF-␤1), hydroxyproline (HYP) concentrations, and level of the mature, nonreducible collagen cross-link hydroxylysylpyridinoline (HP) in diaphragm muscle from 12-week-old mdx mice. Diaphragm muscle from untreated mdx mice had a significantly higher level of TGF-␤1, HYP, and HP cross-link compared with normal C57BL/10J (control) mice. Prednisone treatment significantly reduced the level of TGF-␤1 and HYP in diaphragm from mdx mice to values similar to control mice, but resulted in a higher level of the HP cross-link compared with untreated mdx mice. These findings indicate that short-term treatment of mdx mice with prednisone can attenuate the fibrotic response in diaphragm muscle, possibly by mediating the level of TGF-␤. Although prednisone was beneficial in preventing collagen accumulation, it resulted in a higher level of the HP cross-link, presumably by decreasing collagen turnover

The purpose of this study was to assess the impact of prednisone treatment for 8 weeks on the level of transforming growth factor‐beta 1 (TGF‐β1), hydroxyproline (HYP) concentrations, and level of the mature, nonreducible collagen cross‐link hydroxylysylpyridinoline (HP) in diaphragm muscle from 12‐week‐old mdx mice. Diaphragm muscle from untreated mdx mice had a significantly higher level of TGF‐β1, HYP, and HP cross‐link compared with normal C57BL/10J (control) mice. Prednisone treatment significantly reduced the level of TGF‐β1 and HYP in diaphragm from mdx mice to values similar to control mice, but resulted in a higher level of the HP cross‐link compared with untreated mdx mice. These findings indicate that short‐term treatment of mdx mice with prednisone can attenuate the fibrotic response in diaphragm muscle, possibly by mediating the level of TGF‐β. Although prednisone was beneficial in preventing collagen accumulation, it resulted in a higher level of the HP cross‐link, presumably by decreasing collagen turnover © 2001 John Wiley & Sons, Inc. Muscle Nerve 24: 428–432, 2001

No abstract