Pirfenidone reduces fibronectin synthesis by cultured human retinal pigment epithelial cells.
OBJECTIVE
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.


CONCLUSIONS
We conclude that the anti-fibrotic effect of pirfenidone may be partly mediated through inhibition of TGF-beta1-induced fibronectin synthesis.
Department of Physiology and Pharmacology, University of Queensland, Brisbane, Australia. zhang@plpk.uq.oz.au
S
S
Zhang
I A
IA
Shiels
J S
JS
Ambler
S M
SM
Taylor
D000970:Antineoplastic Agents / Q000494:pharmacology*; D002478:Cells, Cultured; D004338:Drug Combinations; D004797:Enzyme-Linked Immunosorbent Assay; D005353:Fibronectins / Q000378:metabolism*; D006801:Humans; D010857:Pigment Epithelium of Eye / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D011728:Pyridones / Q000494:pharmacology*; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors / Q000494:pharmacology
D000970:Antineoplastic Agents; D004338:Drug Combinations; D005353:Fibronectins; D011728:Pyridones; D016212:Transforming Growth Factor beta; C093844:pirfenidone