Fibrogenic cytokines and extent of fibrosis in muscle of dogs with X-linked golden retriever muscular dystrophy

• Published in: Neuromuscular disorders : NMD 2002-11, Vol.12 (9), p.828-835
• Main Authors: Passerini, Laura, Bernasconi, Pia, Baggi, Fulvio, Confalonieri, Paolo, Cozzi, Francesca, Cornelio, Ferdinando, Mantegazza, Renato
• Format: Article
• Language: English
• Subjects: Age Factors; Animals; Base Sequence; Collagen - genetics; Collagen - metabolism; Connective Tissue Growth Factor; Cytokines - genetics; Cytokines - metabolism; Disease Models, Animal; Dogs; Duchenne muscular dystrophy; Extracellular matrix; Female; Fibrosis - etiology; Genetic Diseases, X-Linked - complications; Genetic Diseases, X-Linked - genetics; Genetic Diseases, X-Linked - metabolism; Golden retriever muscular dystrophy; Immediate-Early Proteins - genetics; Immediate-Early Proteins - metabolism; Immunohistochemistry; Intercellular Signaling Peptides and Proteins - genetics; Intercellular Signaling Peptides and Proteins - metabolism; Male; Muscular Dystrophy, Duchenne - complications; Muscular Dystrophy, Duchenne - genetics; Muscular Dystrophy, Duchenne - metabolism; Polymerase Chain Reaction; RNA, Messenger - metabolism; Transforming Growth Factor beta - genetics; Transforming Growth Factor beta - metabolism; Transforming Growth Factor beta1; Transforming growth factor-β1
• ISSN: 0960-8966; 1873-2364
• DOI: 10.1016/S0960-8966(02)00071-8

Fibrosis in Duchenne muscular dystrophy patients' muscle seems to be mediated by fibrogenic cytokines, particularly transforming growth factor-β1. Golden retriever muscular dystrophy is a model of Duchenne dystrophy characterised by severe myopathy and muscle fibrosis. We evaluated mRNA levels and protein distribution of transforming growth factor-β1, connective tissue growth factor and collagens in muscle of golden retriever muscular dystrophy dogs at different ages. Fibrosis occurs early in golden retriever muscular dystrophy dogs and transforming growth factor-β1 levels tend to be high up to 60 days of age ( P=0.019 at 30 days), suggesting that transforming growth factor-β1 is involved in the early stages of fibrosis. We also found greater expression of connective tissue growth factor in golden retriever muscular dystrophy than control muscle ( P=0.0065 at 30 days), suggesting involvement of this molecule in fibrosis progression. Our findings sustain the hypothesis that cytokines are actively involved in fibrosis in golden retriever muscular dystrophy, as it seems to be in humans, and confirm the utility of this model for investigating new therapeutic approaches for Duchenne dystrophy.