Skeletal muscle cells express the profibrotic cytokine connective tissue growth factor (CTGF/CCN2), which induces their dedifferentiation

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...

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Authors: Vial. C; Zúñiga, L.M.; Cabello-Verrugio, C.; Cañón, P.; Fadic, R.; Brandan, E.
Format: Article
Status:Published version
Publication date:2008
Country:Chile
Institution:Agencia Nacional de Investigación y Desarrollo
Repository:Articulos_ANID
Language:English
OAI Identifier:oai:repositorio.anid.cl:10533/236904
Online Access:https://hdl.handle.net/10533/236904
Access Level:Open access
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author Vial. C
author2 Zúñiga, L.M.
Cabello-Verrugio, C.
Cañón, P.
Fadic, R.
Brandan, E.
author2_role author
author
author
author
author
author_browse Brandan, E.
Cabello-Verrugio, C.
Cañón, P.
Fadic, R.
Vial. C
Zúñiga, L.M.
author_facet Vial. C
Zúñiga, L.M.
Cabello-Verrugio, C.
Cañón, P.
Fadic, R.
Brandan, E.
author_role author
collection Articulos_ANID
description 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-beta (TGF-beta) and lysophosphatidic acid (LPA). CTGF induced several ECM constituents such as fibronectin, collagen type I and alpha4, 5, 6, and beta1 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.
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publishDate 2008
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spelling Skeletal muscle cells express the profibrotic cytokine connective tissue growth factor (CTGF/CCN2), which induces their dedifferentiation J Cell Physiol Vial. C Zúñiga, L.M. Cabello-Verrugio, C. Cañón, P. Fadic, R. Brandan, E. 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-beta (TGF-beta) and lysophosphatidic acid (LPA). CTGF induced several ECM constituents such as fibronectin, collagen type I and alpha4, 5, 6, and beta1 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. FONDAP 13980001 WOS:000254887100014 https://hdl.handle.net/10533/236904
spellingShingle Skeletal muscle cells express the profibrotic cytokine connective tissue growth factor (CTGF/CCN2), which induces their dedifferentiation
Vial. C
status_str publishedVersion
title Skeletal muscle cells express the profibrotic cytokine connective tissue growth factor (CTGF/CCN2), which induces their dedifferentiation
title_full Skeletal muscle cells express the profibrotic cytokine connective tissue growth factor (CTGF/CCN2), which induces their dedifferentiation
title_fullStr Skeletal muscle cells express the profibrotic cytokine connective tissue growth factor (CTGF/CCN2), which induces their dedifferentiation
title_full_unstemmed Skeletal muscle cells express the profibrotic cytokine connective tissue growth factor (CTGF/CCN2), which induces their dedifferentiation
title_short Skeletal muscle cells express the profibrotic cytokine connective tissue growth factor (CTGF/CCN2), which induces their dedifferentiation
title_sort Skeletal muscle cells express the profibrotic cytokine connective tissue growth factor (CTGF/CCN2), which induces their dedifferentiation
url https://hdl.handle.net/10533/236904