Impact of prednisone on TGF‐β1 and collagen in diaphragm muscle from mdx mice

Abstract

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

A Multidisciplinary Evaluation of the Effectiveness of Cyclosporine A in Dystrophic Mdx Mice

“…It is important to underline that CsA is known to exert a profibrotic activity in many organs by enhancing the expression of TGF-␤. 30,37,38 Thus our findings suggest that the CsA-induced reduction of fibrotic events occurs through an indirect mechanism, ie, the reduction of the inflammatory state. Many of the parameters of mdx limb muscles worsened by exercise, including the impairment in chloride channel function observed in EDL muscle fibers (see below), were all similarly ameliorated by CsA treatment, suggesting that their alteration may be because of a general event aggravated by exercise and sensitive to CsA, such as inflammation induced by mechanical stress.…”

“…30 For determination of TGF-␤1 transcript, total RNA was extracted from 10 to 20 mg of muscle biopsy using RNAzol B reagent (Ambion Inc., Austin, TX). One g of total RNA was reverse-transcribed according to the manufacturer's instructions and the cDNA stored at Ϫ20°C pending polymerase chain reaction (PCR) amplification.…”

“…CsA, as well as other immunosuppressants, has been reported to exert a profibrotic action in many tissues, 30,37,38 a mechanism that may oppose to the amelioration of the histological picture. The connective tissue present in the mdx GC muscles belonging to the various groups was determined in H&E sections.…”

Laparoscopic guided local injection in the X-linked muscular dystrophy mouse (mdx) diaphragm. An advance in experimental therapies for Duchenne Muscular Dystrophy

“…In the mdx, the limb skeletal muscle exhibits an initial periods of severe necrosis at 3-4weeks of age lifespan, however the limb muscles of mdx mice undergo sufficient muscle fiber regeneration to compensate for the continued injury to fibers and muscle fiber degeneration. Although the diaphragm muscle exhibits progressive deterioration, similar to human DMD 5,10,11 .…”

Duchenne muscular dystrophy: quality of life among 95 patients evaluated using the Life Satisfaction Index for Adolescents

“…Among patients with DMD, steroid therapy delays the loss of muscle strength and respiratory capacity [10][11][12] . Steroid therapy improves muscle strength within two to four months after beginning the treatment, and it helps to maintain independent walking for at least two more years 13 .…”