Pirfenidone reduces fibronectin synthesis by cultured human retinal pigment epithelial cells

Aust N Z J Ophthalmol. 1998 May;26 Suppl 1:S74-6. doi: 10.1111/j.1442-9071.1998.tb01380.x.

Abstract

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)-beta1. 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-beta1.

Methods: Primary human RPE cultures were used. Treatments included TGF-beta1, pirfenidone and pirfenidone with TGF-beta1. After 72 h treatments, cell growth was determined by cell counting and fibronectin was measured by ELISA.

Results: Transforming growth factor-beta1 (1-10 ng/mL) increased the production of soluble fibronectin, while pirfenidone (300 micromol/L) significantly reduced the TGF-beta1-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-beta1-induced fibronectin synthesis.

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Cells, Cultured
  • Drug Combinations
  • Enzyme-Linked Immunosorbent Assay
  • Fibronectins / metabolism*
  • Humans
  • Pigment Epithelium of Eye / cytology
  • Pigment Epithelium of Eye / drug effects*
  • Pigment Epithelium of Eye / metabolism
  • Pyridones / pharmacology*
  • Transforming Growth Factor beta / antagonists & inhibitors
  • Transforming Growth Factor beta / pharmacology

Substances

  • Antineoplastic Agents
  • Drug Combinations
  • Fibronectins
  • Pyridones
  • Transforming Growth Factor beta
  • pirfenidone