Speaker: Enrique Brandan, PhD
Departamento de Biología Celular
Facultad de Ciencias Biológicas
P. Universidad Católica de Chile
Santiago, Chile

Wednesday, 1 October 2008, Sala Duoda - Filosofia Building

Abstract

Duchenne Muscular dystrophy (DMD) is the most severe myopathy characterized by degeneration of skeletal muscle fibers and its replacement by connective tissue producing fibrosis. Connective tissue grow th factor (CTGF/CCN-2), one of the main inducers of fibrosis is increased in skeletal muscle of patients w ith DMD. Diverse extracellular growth factors have been proposed to modulate the levels of CTGF, regulating the beginning and progression of fibrosis. Among them transforming growth factor beta (TGF-β) which is augmented is skeletal muscle of DMD. In skeletal muscle cells, we have demonstrated that CTGF expression is increased by TGF-β. A novel regulator of TGF-β activity is decorin, a soluble proteoglycan present in skeletal muscle w hich is endocytosed through its receptor LD L-related prtein-1 (LRP-1). In this seminar we will present evidence of the participation of decorin and its receptor LRP-1 in the regulation of TGF-β activity in skeletal muscle cells. Experiments using myoblasts lacking decorin, in which the levels of LRP-1 were diminished by means of siRNA, suggest that decorin favors TGF-β dependent signaling through a mechanism that involves to LRP-1. At the intracellular level, the TGF-β Smad dependent signaling pathw ay w as not altered by the absence of decorin and/or LRP¬1, which suggests the participation of a non canonical signaling pathway. CTGF a recent discovered profibrotic factor is augmented in DMD and induce des-differentiation of skeletal muscle cells together with an increase of fibrotic constituents. Evidence suggesting that decorin interacts and inhibits CTGF profibrotic activity will be presented.

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