Pirfenidone Inhibits Transforming Growth Factor β1-induced Extracellular Matrix Production in Nasal Polyp-derived Fibroblasts. Issue 6 (November 2015)

• Record Type: Journal Article
• Authors: Shin, Jae-Min; Park, Joo-Hoo; Park, Il-Ho; Lee, Heung-Man
• Is Part Of: American journal of rhinology & allergy. Volume 29:Issue 6(2015)
• Page Start: 408
• Page End: 413
• Publication Date: 2015-11
• Subjects: Nose -- Periodicals; Allergy -- Periodicals; 616.21005
• DOI: 10.2500/ajra.2015.29.4221
• Languages: English
• ISSNs: 1945-8924

Abstract

Purpose: Pirfenidone has been shown to have antifibrotic and anti-inflammatory effects in the lungs. The purpose of this study was to evaluate the inhibitory effects of pirfenidone on transforming growth factor (TGF)-β1-induced myofibroblast differentiation and extracellular matrix accumulation. We also determined the molecular mechanisms of pirfenidone in nasal polyp-derived fibroblasts (NPDF). Methods: NPDFs were isolated from nasal polyps from eight patients who had chronic rhinosinusitis with nasal polyp. Pirfenidone was used to treat TGF-β1-induced NPDFs. Cytotoxicity was evaluated by using a 3-(4, 5-dimethylthiazol-2yl)-2, 5-diphenyl-tetrazolium bromide assay. Fibroblast migration was evaluated with scratch assays. Expression levels of α-smooth muscle actin (SMA), fibronectin, and phosphorylated Smad2/3 were determined by Western blot and/or reverse transcription-polymerase chain reaction and immunofluorescent staining. Total collagen production was analyzed with the Sircol collagen assay and contractile activity was measured by a collagen gel contraction assay. Results: Pirfenidone (0-2 mg/mL) has no significant cytotoxic effects in TGF-β1-induced NPDFs. Migration of NPDFs was significantly inhibited by pirfenidone treatment. The expression levels of α-SMA and fibronectin were significantly reduced in pirfenidone-treated NPDFs. Collagen contraction and production were also significantly decreased by pirfenidone treatment. Finally, pirfenidone significantly inhibited phosphorylation of the Smad2/3 pathway in TGF-β1-induced NPDFs. Conclusions: Pirfenidone has an inhibitory effect on TGF-β1-induced migration, myofibroblast differentiation (α-SMA), extracellular matrix accumulation, and collagen contraction by blocking the phosphorylation of Smad2/3 pathways in NPDFs. Thus, pirfenidone may inhibit TGF-β1-induced extracellular matrix by regulating Smad2/3.