T and B lymphocyte depletion has a marked effect on the fibrosis of dystrophic skeletal muscles in the scid/mdx mouse

Journal of Pathology - Tập 213 Số 2 - Trang 229-238 - 2007
Andrea Farini1, Mirella Meregalli1, M. Belicchi1, Maurizio Battistelli1, D. Parolini1, Giuseppe D’Antona2, Manuela Gavina1, Linda Ottoboni3, Gabriela Constantin3, Roberto Bottinelli2, Yvan Torrente1
1Fondazione IRCCS Ospedale Maggiore Policlinico of Milan, Department of Neurological Sciences, Dino Ferrari Center, University of Milan, Italy
2Department of Experimental Medicine, Human Physiology Unit, University of Pavia, Italy
3Department of Pathology, Division of General Pathology, University of Verona, Strada Le Grazie 8, 37134 Verona, Italy

Tóm tắt

AbstractAbnormal 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‐β1 expression. Significant reduction of fibrosis and TGF‐β1 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‐β1, suggesting the importance of modulation of the immune system in DMD. Copyright © 2007 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

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Journal of Pathology

Tập 213 Số 2

229-238

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