Tetrandrine Suppresses Activation of Human Subconjunctival Fibroblasts In Vitro

• Published in: Current eye research 2008-01, Vol.33 (7), p.559-565
• Main Authors: Kitano, Ai, Yamanaka, Osamu, Ikeda, Kazuo, Ishida-Nishikawa, Iku, Okada, Yuka, Shirai, Kumi, Saika, Shizuya
• Format: Article
• Language: English
• Subjects: Actins - metabolism; Benzylisoquinolines - pharmacology; Blotting, Western; Cell Movement - drug effects; Cell Proliferation - drug effects; Cells, Cultured; Collagen Type I - genetics; Collagen Type I - metabolism; Collagen Type III - genetics; Collagen Type III - metabolism; Conjunctiva - cytology; Drugs, Chinese Herbal - pharmacology; Enzyme-Linked Immunosorbent Assay; Fibroblasts - drug effects; Fibroblasts - metabolism; Fibronectins - metabolism; fibrosis; Fluorescent Antibody Technique, Indirect; Humans; Immunosuppressive Agents - pharmacology; myofibroblast; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - metabolism; Signal Transduction; Smad2 Protein - metabolism; Smad7 Protein - metabolism; subconjunctival fibroblast; tetrandrine; Transforming Growth Factor beta1 - pharmacology; transforming growth factor β
• ISSN: 0271-3683; 1460-2202
• DOI: 10.1080/02713680802220817

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.