Pirfenidone inhibits proliferation, migration, and collagen contraction of Human Tenon's Fibroblasts in vitro
Xianchai Lin 1,
Minbin Yu 1*,
Kaili Wu 1,
Hongzhi Yuan 1,
and
Hua Zhong 1
1 State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China
* To whom correspondence should be addressed. E-mail: max-yu{at}tom.com.
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Abstract |
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Purpose: To investigate the role of pirfenidone, a novel antifibrotic agent, on proliferation, migration, and collagen contraction of human Tenon's fibroblasts (HTFs).
Methods: After treatment of HTFs with pirfenidone, cell proliferation was measured by MTT assay. Cell migration was investigated by Scratch assay. Contractility was evaluated in fibroblast-populated collagen gels. Cell viability was determined by trypan blue exclusion assay. The expressions of TGF-
1, -2, and -3 were estimated with RT-PCR, Western blot, and immunofluorescence analyses.
Results: Pirfenidone induced significant inhibitions of HTFs proliferation, migration, and collagen contraction in a dose-dependent manner. After treatment with different concentrations of pirfenidone (0.15, 0.3, and 1mg/ml) for 24 and 72 hours, cell viability showed no difference between treatment and control groups. After 24 hours of treatment with pirfenidone, HTFs showed decreased mRNA and protein levels of TGF-1, -2, and -3 with a dose-dependent manner.
Conclusions: These findings indicate that pirfenidone inhibits proliferation, migration and collagen contraction of HTFs at nontoxic concentrations. Decrease in autocrine TGF-s signaling may have roles in the effects of pirfenidone.
Key Words:
pirfenidone, glaucoma surgery, human Tenon's fibroblast, transformed growth factor-beta
