Effects of pirfenidone on proliferation, migration, and collagen contraction of human Tenon's fibroblasts in vitro.

PURPOSE: To investigate the effect 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 expression of TGF-beta1, -beta2, and -beta3 was estimated with RT-PCR, Western blot, and immunofluorescence analyses.

RESULTS: Pirfenidone induced significant dose-dependent inhibition of HTF proliferation and migration and collagen contraction. After treatment with different concentrations of pirfenidone (0.15, 0.3, and 1 mg/mL) for 24 and 72 hours, cell viability was not different in the treatment and control groups. After 24 hours of treatment with pirfenidone, HTFs showed dose-dependent decreases in mRNA and protein levels of TGF-beta1, -beta2, and -beta3.

CONCLUSIONS: These findings indicate that pirfenidone inhibits proliferation, migration, and collagen contraction of HTFs at nontoxic concentrations. A decrease in autocrine TGF-beta signaling may have a role in the effects of pirfenidone.