Fibrogenic cytokines and extent of fibrosis in muscle of dogs with X-linked golden retriever muscular dystrophy.
Fibrosis in Duchenne muscular dystrophy patients' muscle seems to be mediated by fibrogenic cytokines, particularly transforming growth factor-beta1. 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-beta1, 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-beta1 levels tend to be high up to 60 days of age (P=0.019 at 30 days), suggesting that transforming growth factor-beta1 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.
Passerini
Laura
L
Myopathology and Immunology Unit, Istituto Nazionale Neurologico 'Carlo Besta', Via Celoria 11, 20133, Milan, Italy.
Bernasconi
Pia
P
Baggi
Fulvio
F
Confalonieri
Paolo
P
Cozzi
Francesca
F
Cornelio
Ferdinando
F
Mantegazza
Renato
R
D000367:Age Factors; D000818:Animals; D001483:Base Sequence; D003094:Collagen / Q000235:genetics / Q000378:metabolism; D055513:Connective Tissue Growth Factor; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D004285:Dogs; D005260:Female; D005355:Fibrosis / Q000209:etiology*; D040181:Genetic Diseases, X-Linked / Q000150:complications / Q000235:genetics / Q000378:metabolism*; D017874:Immediate-Early Proteins / Q000235:genetics / Q000378:metabolism; D007150:Immunohistochemistry; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D008297:Male; D020388:Muscular Dystrophy, Duchenne / Q000150:complications / Q000235:genetics / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism; D053773:Transforming Growth Factor beta1
C526317:CCN2 protein, human; D016207:Cytokines; D017874:Immediate-Early Proteins; D036341:Intercellular Signaling Peptides and Proteins; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D055513:Connective Tissue Growth Factor; D003094:Collagen