Pirfenidone reduces fibronectin synthesis by cultured human retinal pigment epithelial cells

Purpose: Pirfenidone is a novel anti-fibrotic drug that has been shown to inhibit fibroblast growth and collagen synthesis induced by transforming growth factor (TGF)-β₁. In the present study we investigated the ability of pirfenidone to moderate fibronectin synthesis by cultured human retinal pigment epithelial (RPE) cells maintained in media containing 1% foetal bovine serum when stimulated with TGF-β₁. Methods: Primary human RPE cultures were used. Treatments included TGF-β₁, pirfenidone and pirfenidone with TGF-β₁. After 72 h treatments, cell growth was determined by cell counting and fibronectin was measured by ELISA. Results: Transforming growth factor-β₁ (1-10 ng/mL) increased the production of soluble fibronectin, while pirfenidone (300 μmol/L) significantly reduced the TGF-β₁-induced synthesis of fibronectin. Pirfenidone alone had no effect on fibronectin synthesis by cultured RPE cells. Conclusion: We conclude that the anti- fibrotic effect of pirfenidone may be partly mediated through inhibition of TGF-β₁-induced fibronectin synthesis.