Localization
and early time course of TGF-beta 1 mRNA expression in dystrophic muscle
Muscle and Nerve, 2004
Luc E. Gosselin, PhD, Jacqueline E.
Williams, BS, Melissa Deering, MS, Daniel Brazeau, PhD, Stephen Koury, PhD,
Daniel A. Martinez, PhD - USA
Fibrosis is a
common pathological feature observed in muscle from patients with Duchenne
muscular dystrophy (DMD). In the dystrophic (mdx) mouse model of DMD,
the diaphragm is more severely affected than other skeletal muscles. The level
of transforming growth factor-beta1 (TGF-beta1), an inflammatory cytokine, is
significantly elevated in mdx diaphragm. However, little is known about
the onset of TGF-beta1 messenger ribonucleic acid (mRNA) expression, or which
cells express the mRNA. In this study, we characterized the location and time
course of expression of TGF-beta1 mRNA in diaphragm from mdx mice.
TGF-beta 1 mRNA was significantly elevated in mdx diaphragm at 6 and 9
but not 12 weeks of age, and these changes corresponded with changes in type I
collagen mRNA and hydroxyproline concentration. Mononucleated cells localized
to areas of fiber necrosis highly expressed the TGF-beta1 transcript in mdx
diaphragm.
Neutralization
of TGF-beta 1 by decorin administration resulted in a 40% reduction in the
level of diaphragm muscle type I collagen mRNA. These findings support a role for TGF-beta1
during the early stages of fibrogenesis in dystrophic diaphragm muscle.
Therapeutic interventions aimed at neutralizing this cytokine may be beneficial
in slowing the development of fibrosis in DMD.