Elevated plasma levels of tissue inhibitors of metalloproteinase-1 and their overexpression in muscle in human and mouse muscular dystrophy

Guilian Sun, Kazuhiro Haginoya, Yoko Chiba, Mitsugu Uematsu, Naomi Hino-Fukuyo, Soichiro Tanaka, Akira Onuma, Kazuie Iinuma, Shigeru Tsuchiya

Research output: Contribution to journalArticlepeer-review

19 Citations (Scopus)

Abstract

To investigate the role of tissue inhibitors of metalloproteinases (TIMPs) in muscular dystrophy, we examined the expression of TIMP-1 using plasma and biopsied muscle from patients with various muscular dystrophies by ELISA, immunohistochemistry, and Western blot analysis. TIMP-1 immunolocalization was also studied in mouse models of muscular dystrophy. Plasma TIMP-1 was elevated and correlated with TGF-β1 in Duchenne muscular dystrophy (DMD) and congenital muscular dystrophy (CMD), but not in Becker muscular dystrophy. In dystrophic human muscles, TIMP-1 was immunopositive in the regenerating and non-regenerating muscle fibers, and interstitial cells that consist of activated fibroblasts and macrophages. TIMP-1 immunoreactivity was also closely associated with TGF-β1. Western blot analysis showed elevated TIMP-1 protein in muscles in DMD. The semiquantitative analysis of TIMP-1 staining intensity and tissue fibrosis showed that TIMP-1 immunoreactivity is closely associated with the extent of tissue fibrosis in human and mouse dystrophic muscles. In conclusion, the present study implied that the TGF-β1-TIMP-1 pathway is activated in dystrophic muscles and the overexpression of TIMP-1 may result in increased deposition of extracellular matrix leading to tissue fibrosis.

Original languageEnglish
Pages (from-to)19-28
Number of pages10
JournalJournal of the neurological sciences
Volume297
Issue number1-2
DOIs
Publication statusPublished - 2010 Oct 15

Keywords

  • Fibrosis
  • Muscular dystrophy
  • Neuromuscular junction
  • Tissue inhibitors of metalloproteinase
  • Transforming growth factor-β1

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

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