[Liver X receptor agonist T0901317 inhibits TGF-β1-induced α-SMA expression in normal human lung fibroblasts]

Nan Fang Yi Ke Da Xue Xue Bao. 2011 May;31(5):744-8.
[Article in Chinese]

Abstract

Objective: To investigate the effect of liver X receptor agonist T0901317 on transforming growth factor-β1 (TGF-β1)-induced expression of α-smooth muscle actin (α-SMA) in normal human lung fibroblasts.

Methods: Primary normal human lung fibroblast isolated from the lung specimens of lung cancer patients by explant culture technique were identified with immunostaining for vimentin and keratin. The cells in passages 4 to 10 were treated with T0901317 and/or TGF-β1, and RT-PCR, Western blotting and immunofluorescence assay were used to detect α-SMA expression in the fibroblasts.

Results: Lung fibroblast expressed vimentin but not keratin. The results of RT-PCR, Western blotting and immunofluorescence assay all showed that normal human lung fibroblasts constitutively expressed α-SMA under baseline condition, and TGF-β1 at 5 ng/ml induced a significant upregulation of α-SMA both at the mRNA and protein levels. Liver X receptor agonist T0901317 (5 µg/ml) significantly inhibited TGF-β1-induced upregulation of α-SMA expression.

Conclusion: Liver X receptor agonist T0901317 can inhibit the upregulation of α-SMA in normal human lung fibroblasts induced by TGF-β1, suggesting the potential value of liver X receptor agonist in the treatment of lung fibrosis.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Actins / metabolism*
  • Cells, Cultured
  • Female
  • Fibroblasts / drug effects*
  • Fibroblasts / metabolism*
  • Humans
  • Hydrocarbons, Fluorinated / pharmacology*
  • Liver X Receptors
  • Lung / cytology
  • Middle Aged
  • Orphan Nuclear Receptors / agonists
  • RNA, Messenger / genetics
  • Sulfonamides / pharmacology*
  • Transforming Growth Factor beta1 / pharmacology*

Substances

  • Actins
  • Hydrocarbons, Fluorinated
  • Liver X Receptors
  • Orphan Nuclear Receptors
  • RNA, Messenger
  • Sulfonamides
  • T0901317
  • Transforming Growth Factor beta1