Chymase mediates paraquat-induced collagen production in human lung fibroblasts

Yaw Dong Lang, Shwu Fen Chang, Leng-Fang Wang, Chung Ming Chen

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Survivors of paraquat poisoning may be left with pulmonary fibrosis and a restrictive type of pulmonary dysfunction. Chymase converts angiotensin (Ang) I to Ang II, which is closely involved with lung fibrosis. The role played by chymase in paraquat-induced lung fibrosis is unclear. We examined the effects of paraquat on chymase, renin-angiotensin system components, and collagen expression in murine and human lung fibroblasts (MRC-5). Lung chymase and collagen type I mRNA and protein expression were significantly increased and angiotensin-converting enzyme (ACE) mRNA and protein expression were comparable between the control and paraquat-treated mice 1 and 3 weeks after administration. Paraquat significantly upregulated angiotensinogen mRNA expression in a dose-dependent manner while ACE activity and protein expression were similar in MRC-5 cells. Furthermore, paraquat enhanced Ang II and collagen type I mRNA and protein expression, α-smooth muscle actin, and chymase protein and chymase small interfering RNA inhibited these effects. The cDNA sequence of chymase in MRC-5 cells is identical to that in human mast cells. This study found increased chymase expression in paraquat-treated human lung fibroblasts and confirmed in vitro and in an in vivo paraquat model of lung fibrosis that chymase generates Ang II and enhances collagen expression. These data suggest a role for chymase in the pathogenesis of paraquat-induced lung fibrosis.

Original languageEnglish
Pages (from-to)19-25
Number of pages7
JournalToxicology Letters
Volume193
Issue number1
DOIs
Publication statusPublished - Mar 1 2010

Keywords

  • Angiotensin
  • Angiotensin-converting enzyme
  • siRNA

ASJC Scopus subject areas

  • Toxicology

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