Abstract:

BACKGROUND: The effect and mechanism of peroxisome proliferator-activated receptor gamma (PPARγ) agonists on transforming growth factor (TGF)-β1-induced fibrotic responses in lung fibroblasts remain unclear, and seldom reported.
OBJECTIVE: To study the effects of PPARγ agonists on TGF-β1-induced fibrotic responses in lung fibroblasts, so as to investigate its effects in preventing pulmonary interstitial fibrosis of silicosis.
METHODS: The pulmonary alveolar macrophage was prepared with 200 mg/L SiO₂ and the supernatants were got. Chinese hamster lung fibroblasts were incubated with the prepared supernatants. Then a cellular model in vitro for studying pulmonary fibrosis induced by SiO₂ was developed. Chinese hamster lung fibroblasts were cultured to observe the effects of the PPARγ ligand (15 d-PGJ2) and its agonists (troglitazone and ciglitazone) on the expression of TGF-β1-induced fibronectin. RT-PCR was used to detect the mRNA expression of fibronectin and Western blotting was used to detect the protein expression of fibronectin.
RESULTS AND CONCLUSION: (1) The expression of TGF-β1 mRNA showed an effect in a dose- (0-5 μg/L) and time-(0-24 hours) dependent manner. (2) PPARγ ligands and agonists reduced the mRNA and protein expressions of fibronectin. Results suggested that PPARγ agonists can inhibit TGF-β1-induced fibronectin synthesis after stimulation by SiO₂ and may play a potential role in preventing pulmonary interstitial fibrosis.