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

A. Farini, M. Meregalli, M. Belicchi, M. Battistelli, D. Parolini, G. D'Antona, M. Gavina, L. Ottoboni, G. Constantin, R. Bottinelli, Y. Torrente

Research output: Contribution to journalArticle

Abstract

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-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.

Original languageEnglish
Pages (from-to)229-238
Number of pages10
JournalJournal of Pathology
Volume213
Issue number2
DOIs
Publication statusPublished - Oct 2007

Fingerprint

Lymphocyte Depletion
Inbred mdx Mouse
Duchenne Muscular Dystrophy
Skeletal Muscle
Fibrosis
B-Lymphocytes
T-Lymphocytes
Muscles
Dystrophin
Muscular Dystrophies
Muscular Diseases
Connective Tissue
Immune System
Necrosis
Enzyme-Linked Immunosorbent Assay
Therapeutics
Research
Proteins

Keywords

  • Duchenne muscular dystrophy (DMD)
  • Fibrosis
  • MDX
  • SCID

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

T and B lymphocyte depletion has a marked effect on the fibrosis of dystrophic skeletal muscles in the scid/mdx mouse. / Farini, A.; Meregalli, M.; Belicchi, M.; Battistelli, M.; Parolini, D.; D'Antona, G.; Gavina, M.; Ottoboni, L.; Constantin, G.; Bottinelli, R.; Torrente, Y.

In: Journal of Pathology, Vol. 213, No. 2, 10.2007, p. 229-238.

Research output: Contribution to journalArticle

Farini, A. ; Meregalli, M. ; Belicchi, M. ; Battistelli, M. ; Parolini, D. ; D'Antona, G. ; Gavina, M. ; Ottoboni, L. ; Constantin, G. ; Bottinelli, R. ; Torrente, Y. / T and B lymphocyte depletion has a marked effect on the fibrosis of dystrophic skeletal muscles in the scid/mdx mouse. In: Journal of Pathology. 2007 ; Vol. 213, No. 2. pp. 229-238.
@article{1aa49666ede24377854666381b3645ea,
title = "T and B lymphocyte depletion has a marked effect on the fibrosis of dystrophic skeletal muscles in the scid/mdx mouse",
abstract = "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-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.",
keywords = "Duchenne muscular dystrophy (DMD), Fibrosis, MDX, SCID",
author = "A. Farini and M. Meregalli and M. Belicchi and M. Battistelli and D. Parolini and G. D'Antona and M. Gavina and L. Ottoboni and G. Constantin and R. Bottinelli and Y. Torrente",
year = "2007",
month = "10",
doi = "10.1002/path.2213",
language = "English",
volume = "213",
pages = "229--238",
journal = "Journal of Pathology",
issn = "0022-3417",
publisher = "John Wiley and Sons Ltd",
number = "2",

}

TY - JOUR

T1 - T and B lymphocyte depletion has a marked effect on the fibrosis of dystrophic skeletal muscles in the scid/mdx mouse

AU - Farini, A.

AU - Meregalli, M.

AU - Belicchi, M.

AU - Battistelli, M.

AU - Parolini, D.

AU - D'Antona, G.

AU - Gavina, M.

AU - Ottoboni, L.

AU - Constantin, G.

AU - Bottinelli, R.

AU - Torrente, Y.

PY - 2007/10

Y1 - 2007/10

N2 - 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-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.

AB - 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-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.

KW - Duchenne muscular dystrophy (DMD)

KW - Fibrosis

KW - MDX

KW - SCID

UR - http://www.scopus.com/inward/record.url?scp=35349000178&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=35349000178&partnerID=8YFLogxK

U2 - 10.1002/path.2213

DO - 10.1002/path.2213

M3 - Article

C2 - 17668421

AN - SCOPUS:35349000178

VL - 213

SP - 229

EP - 238

JO - Journal of Pathology

JF - Journal of Pathology

SN - 0022-3417

IS - 2

ER -