T-cell-dependent fibrosis in the mdx dystrophic mouse.
In Duchenne muscular dystrophy patients, the pathological hallmark of the disease, namely, the chronic accumulation of sclerotic scar tissue in the interstitial space of skeletal muscle is attributed to manifestation of secondary pathological processes. Such anomalous generation of matrix protein is thought to be driven by the continuous degeneration and regeneration of muscle both in Duchenne Muscular Dystrophy and in the mdx mouse homolog. We examined mdx and the control strain C57bl/10 mice over a range of ages with respect to the amounts of collagen present in muscles and other organs, finding that the mdx have significantly higher collagen content at later time points in their kidney and lung as well as their muscles. Surprisingly, when we bred the mdx mice on the nu/nu background, the time course of fibrogenesis was modified depending on the tissue and the collagen content was significantly different in age-matched mice. Transplantation of normal thymic tissue into the mdx-nu/nu mice replenished their T-cells and concomitantly altered the collagen content in their tissues to levels comparable with those in immunocompetent mdx mice. This suggests that T-cells play a role in the onset of the fibrotic events that undermines the ability of dystrophic muscle to regenerate.
Morrison
J
J
Muscle Cell Biology Group, MRC Clinical Sciences Centre, Imperial College School of Medicine, Hammersmith Hospital, London, United Kingdom.
Lu
Q L
QL
Pastoret
C
C
Partridge
T
T
Bou-Gharios
G
G
D000375:Aging; D000818:Animals; D016326:Extracellular Matrix Proteins / Q000032:analysis / Q000378:metabolism; D005355:Fibrosis; D006909:Hydroxyproline / Q000032:analysis; D051379:Mice; D008810:Mice, Inbred C57BL; D018101:Mice, Inbred mdx; D008819:Mice, Nude; D018482:Muscle, Skeletal / Q000276:immunology / Q000473:pathology* / Q000502:physiology; D009137:Muscular Dystrophy, Animal / Q000276:immunology* / Q000473:pathology*; D009928:Organ Specificity; D012038:Regeneration; D013601:T-Lymphocytes / Q000276:immunology* / Q000473:pathology
D016326:Extracellular Matrix Proteins; D006909:Hydroxyproline