The fibrinolitys system in muscle regeneration and dystrophy-

Authors
B. Vidal Iglesias.


Lab
Universitat Pompeu Fabra. Departament de Ciències Experimentals i de la Salut, Barcelona, Spain.

Journal
Tesis Doctorals en Xarxa - Universitat Pompeu Fabra

Abstract
Duchenne muscular dystrophy (DMD) is a fatal degenerative disorder of locomotor and respiratory muscles, in which myofibers are progressively replaced by non-muscular fibrotic tissue. Here, we show that fibrin/ogen accumulates in dystrophic muscles of DMD patients and of the mdx mouse model of DMD. Genetic loss or pharmacological depletion of fibrin/ogen in mdx mice attenuated muscular dystrophy progression and improved locomotor capacity. More importantly, fibrin/ogen depletion reduced fibrosis in mdx mouse diaphragm. Our data indicate that fibrin/ogen, through induction of IL-1 Ò, drives the synthesis of TGF Ò by mdx macrophages, which in turn, induces collagen production in mdx fibroblasts. Fibrin/ogen-produced TGF Ò further amplifies collagen accumulation through recruitment and activation of pro-fibrotic alternatively activated macrophages. Fibrin/ogen also stimulated collagen synthesis directly in mdx fibroblasts, via Ñv Ò3 integrin engagement. In addition, when analyzing a group of 39 DMD patients, fibrin/ogen accumulation in locomotor muscles was found associated with fibrosis and disease severity. These data unveil a novel role of fibrin/ogen in muscular dystrophy and, importantly, in the replacement of muscle by fibrotic tissue.

BIOSEB Instruments Used:
Grip strength test (BIO-GS3)

Related products

Publication request

Thank you for your interest in our product range and your request for this publication, which will be sent to you if the research team and the journal allow it. Our commercial team will contact you as soon as possible.