T and B lymphocyte depletion has a marked effect on the fibrosis of dystrophic skeletal muscles in the scid/mdx mouse.
Abnormal connective tissue proliferation following muscle degeneration is a major pathological feature of Duchenne muscular dystrophy (DMD), a genetic myopathy due to lack of the sarcolemmal dystrophin protein. Since this fibrotic proliferation is likely to be a major obstacle to the efficacy of future therapies, research is needed to understand and prevent the fibrotic process in order to develop an effective treatment. Murine muscular dystrophy (mdx) is genetically homologous to DMD, and histopatological alterations are comparable to those of the muscles of patients with DMD. To investigate the development of fibrosis, we bred the mdx mouse with the scid immunodepressed mouse and analysed fibrosis histologically; we used ELISA analysis to determine TGF-beta1 expression. Significant reduction of fibrosis and TGF-beta1 expression was found in the muscles of the scid/mdx mice. However, we observed similar centrally located nuclei, necrosis, muscle degeneration and muscle force compared to the mdx animals. These data demonstrate a correlation between the absence of B and T lymphocytes and loss of fibrosis accompanied by reduction of TGF-beta1, suggesting the importance of modulation of the immune system in DMD.
Farini
A
A
Fondazione IRCCS Ospedale Maggiore Policlinico of Milan, Department of Neurological Sciences, Dino Ferrari Center, University of Milan, Italy.
Meregalli
M
M
Belicchi
M
M
Battistelli
M
M
Parolini
D
D
D'Antona
G
G
Gavina
M
M
Ottoboni
L
L
Constantin
G
G
Bottinelli
R
R
Torrente
Y
Y
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D015815:Cell Adhesion Molecules / Q000378:metabolism; D003433:Crosses, Genetic; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005355:Fibrosis / Q000276:immunology; D008297:Male; D051379:Mice; D018101:Mice, Inbred mdx; D016513:Mice, SCID; D018485:Muscle Fibers, Skeletal / Q000378:metabolism / Q000473:pathology; D018482:Muscle, Skeletal / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D009137:Muscular Dystrophy, Animal / Q000276:immunology* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D020388:Muscular Dystrophy, Duchenne / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D010375:Pedigree; D013601:T-Lymphocytes / Q000276:immunology*
D015815:Cell Adhesion Molecules