Rosiglitazone inhibits migration, proliferation, and phenotypic differentiation in cultured human lung fibroblasts.
Recent studies have indicated that peroxisome proliferator-activated receptor gamma (PPARgamma) is capable of modulating inflammation, which prompted us to investigate the potential of PPARgamma ligands as lung protective agents in pulmonary fibrosis. The present study was undertaken to investigate the effects of rosiglitazone (RSG), a highly potent ligand of PPARgamma, on migration, proliferation, and phenotypic differentiation of human lung fibroblasts (MRC-5) and to explore its potential for therapy of pulmonary fibrosis. The cell migration potential was observed in a scratch wound model. Cell proliferation was determined by the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) method, immunocytochemical staining, and flow cytometry, and protein expression by Western blot analysis. RSG slowed cell migration distance induced by fetal bovine serum (FBS), decreased cell proliferation initiated by FBS or platelet-derived growth factor-BB (PDGF-BB), and decreased alpha-smooth muscle actin (alpha-SMA) protein expression induced by transforming growth factor-beta1 (TGF-beta1). In addition, RSG incubation reduced the ratio of phospho-extracellular signal-regulated kinases 1/2 (p-ERK1/2) to ERK1/2 expression stimulated by FBS, PDGF-BB, and TGF-beta1. These findings show that RSG treatment inhibits lung fibroblast migration and proliferation and myofibroblast transdifferentiation stimulated by FBS and growth factors in vitro, which suggests that PPARgamma agonists could antagonize pulmonary fibrosis and have potential for therapeutic application in pulmonary fibrosis.
Lin
Qing
Q
Department of Geriatrics, Peking University First Hospital, Xishiku Street No. 8, Beijing, People's Republic of China.
Fang
Li-Ping
LP
Zhou
Wei-Wei
WW
Liu
Xin-Min
XM
D000077214:Becaplermin; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D054338:Cell Transdifferentiation / Q000187:drug effects*; D002478:Cells, Cultured; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005347:Fibroblasts / Q000187:drug effects*; D006801:Humans; D008168:Lung / Q000166:cytology; D047495:PPAR gamma / Q000819:agonists*; D010641:Phenotype; D010766:Phosphorylation; D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D011658:Pulmonary Fibrosis / Q000209:etiology*; D000077154:Rosiglitazone; D044967:Serum; D045162:Thiazolidinediones / Q000494:pharmacology*; D053773:Transforming Growth Factor beta1
D047495:PPAR gamma; D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D045162:Thiazolidinediones; D053773:Transforming Growth Factor beta1; D000077154:Rosiglitazone; D000077214:Becaplermin; D048049:Extracellular Signal-Regulated MAP Kinases