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Skeletal muscle cells express the profibrotic cytokine connective tissue growth factor (CTGF/CCN2), which induces their dedifferentiation
Author(s) -
Vial Cecilia,
Zúñiga Lidia Miriam,
CabelloVerrugio Claudio,
Cañón Pablo,
Fadic Ricardo,
Brandan Enrique
Publication year - 2008
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/jcp.21324
Subject(s) - ctgf , myogenesis , myod , myocyte , connective tissue , growth factor , extracellular matrix , fibrosis , biology , myogenin , skeletal muscle , microbiology and biotechnology , endocrinology , medicine , desmin , myosin , fibronectin , immunology , vimentin , genetics , receptor , immunohistochemistry
Fibrotic disorders are typified by excessive connective tissue and extracellular matrix (ECM) deposition that precludes normal healing processes of different tissues. Connective tissue growth factor (CTGF) seems to be involved in the fibrotic response. Several muscular dystrophies are characterized by a progressive weakness and wasting of the musculature, and by extensive fibrosis. However, the exact role of CTGF in skeletal muscle is unknown. Here we show that myoblasts and myotubes are able to synthesize CTGF in response to transforming growth factor type‐β (TGF‐β) and lysophosphatidic acid (LPA). CTGF induced several ECM constituents such as fibronectin, collagen type I and α4, 5, 6, and β1 integrin subunits in myoblasts and myotubes. CTGF had an important inhibitory effect on muscle differentiation evaluated by the decrease in the nuclear translocation of the early muscle regulatory factor myogenin and myosin. Remarkable, CTGF treatment of myoblasts induced their dedifferentiation, characterized by down regulating MyoD and desmin, two markers of committed myoblasts, together with a strong reorganization of cytoskeletal filaments. These results provide novel evidence for the underlying mechanisms and participation of skeletal muscle cells in the synthesis and role of CTGF inducing fibrosis, inhibiting myogenesis and dedifferentiating myoblasts. J. Cell. Physiol. 215: 410–421, 2008. © 2007 Wiley‐Liss, Inc.