Tetrandrine Suppresses Activation of Human Subconjunctival Fibroblasts In Vitro

Abstract

Purpose: To investigate the effect of tetrandrine on activation of human subconjunctival fibroblasts (SCFs) in vitro. Methods: Effects of tetrandrine on proliferation, matrix expression, myofibroblast generation, and cell migration of SCF were examined in SCF cultures. Tetrandrine effect on TGFβ 1/Smad2 signal and Smad7 expression was examined. Migration was evaluated by in vitro defect closure in a monolayer cell culture. Western blotting and immunocytochemistry were used. Results: Tetrandrine suppressed wound-induced cell migration (defect closure) and myofibroblast generation, but not cell proliferation in SCF cultures. It also decreased expression of fibronectin, collagen I, and α SMA. Adding tetrandrine increased protein level of Smad7 and suppressed Smad2 signal. Conclusion: Tetrandrine suppresses Smad2 signal and fibrogenic responses in SCFs in association with Smad7 up-regulation, suggesting its potential therapeutic value to prevent excess scarring/fibrosis in conjunctiva following trabeculectomy or in patients with severe conjunctival inflammation.

KEYWORDS:

• fibrosis
• myofibroblast
• subconjunctival fibroblast
• tetrandrine
• transforming growth factor β