Title: Fibrinogen drives dystrophic muscle fibrosis via a TGFbeta/alternative macrophage activation pathway
Authors: Vidal, Berta ×
Serrano, Antonio L
Tjwa, Marc
Suelves, Mònica
Ardite, Esther
De Mori, Roberta
Baeza-Raja, Bernat
Martínez de Lagrán, María
Lafuste, Peggy
Ruiz-Bonilla, Vanessa
Jardí, Mercè
Gherardi, Romain
Christov, Christo
Dierssen, Mara
Carmeliet, Peter
Degen, Jay L
Dewerchin, Mieke
Muñoz-Cánoves, Pura #
Issue Date: Jul-2008
Publisher: Cold spring harbor lab press, publications dept
Series Title: Genes & development vol:22 issue:13 pages:1747-52
Abstract: In the fatal degenerative Duchenne muscular dystrophy (DMD), skeletal muscle is progressively replaced by fibrotic tissue. Here, we show that fibrinogen accumulates in dystrophic muscles of DMD patients and mdx mice. Genetic loss or pharmacological depletion of fibrinogen in these mice reduced fibrosis and dystrophy progression. Our results demonstrate that fibrinogen-Mac-1 receptor binding, through induction of IL-1beta, drives the synthesis of transforming growth factor-beta (TGFbeta) by mdx macrophages, which in turn induces collagen production in mdx fibroblasts. Fibrinogen-produced TGFbeta further amplifies collagen accumulation through activation of profibrotic alternatively activated macrophages. Fibrinogen, by engaging its alphavbeta3 receptor on fibroblasts, also directly promotes collagen synthesis. These data unveil a profibrotic role of fibrinogen deposition in muscle dystrophy.
ISSN: 0890-9369
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Molecular and Vascular Biology
Vesalius Research Centre (-)
Laboratory of Angiogenesis and Vascular Metabolism (Vesalius Research Center) (+)
× corresponding author
# (joint) last author

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