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Increased expression of IGF‐binding protein‐5 in Duchenne Muscular Dystrophy (DMD) fibroblasts correlates with the fibroblast‐induced downregulation of DMD myoblast growth: An in vitro analysis
Author(s) -
Melone Mariarosa A.B.,
Peluso Gianfranco,
Galderisi Umberto,
Petillo Orsolina,
Cotrufo Roberto
Publication year - 2000
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/1097-4652(200010)185:1<143::aid-jcp14>3.0.co;2-u
Subject(s) - paracrine signalling , fibroblast , duchenne muscular dystrophy , microbiology and biotechnology , myocyte , cell growth , fibroblast growth factor receptor 3 , fibroblast growth factor receptor 4 , biology , transfection , fibroblast growth factor , cell culture , chemistry , fibroblast growth factor receptor , biochemistry , genetics , receptor
In DMD the progressive loss of muscle ability and concomitant increasing fibrosis might originate from, besides other causes, the fibroblast paracrine inhibition of satellite cell “growth.” In this study we report that in myoblast/fibroblast coculture experiments, the presence of DMD fibroblasts negatively interfered with DMD myoblast growth to an extent directly proportional to the percentage of DMD fibroblasts present in the mixed‐cell cultures. Moreover, the observation that media conditioned with proliferating DMD fibroblasts inhibited the growth of DMD myoblasts more seriously than did control fibroblast‐conditioned media suggested a paracrine effect by diffusible factors. IGF‐binding proteins could act as such diffusible factors; in fact, IGFBP‐5 transcript increased threefold in DMD fibroblasts proliferating in DMD muscle extracts, whereas IGFBP‐3 mRNA decreased. In addition, high levels of IGFBP‐5 protein were detected in DMD fibroblast‐conditioned media. In neutralizing IGFBP‐5 in DMD fibroblast‐conditioned media by means of specific antibodies, or inhibiting IGFBP‐5 gene expression in DMD fibroblasts by means of oligo antisense, the fibroblast‐conditioned media lost inhibitory power over DMD myoblast proliferation. J. Cell. Physiol. 185:143–153, 2000. © 2000 Wiley‐Liss, Inc.