Tetrandrine suppresses activation of human subconjunctival fibroblasts in vitro

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 TGF beta 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 alpha 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.