Tetrandrine suppresses activation of human subconjunctival fibroblasts in vitro

Tetrandrine suppresses activation of human subconjunctival fibroblasts in vitro
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DOI:
10.1080/02713680802220817
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发表时间:
2008-01-01
影响因子:
2
通讯作者:
Saika, Shizuya
Saika, Shizuya
中科院分区:
医学4区
文献类型:
--
作者:
Kitano, Ai;Yamanaka, Osamu;Saika, Shizuya

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目的:探讨粉防己碱对人结膜下成纤维细胞(SCFs)体外活化的影响。方法:在SCF培养中观察粉防己碱对SCF增殖、基质表达、成肌细胞生成和细胞迁移的影响。检测粉防己碱对TGF β 1/Smad2信号及Smad7表达的影响。通过在体外单层细胞培养中闭合缺陷来评估迁移。采用免疫印迹和免疫细胞化学方法。结果:粉防己碱抑制伤口诱导的细胞迁移(缺损闭合)和肌成纤维细胞生成,但不抑制SCF培养中的细胞增殖。它还能降低纤维连接蛋白、I型胶原和α - SMA的表达。粉防己碱增加Smad7蛋白水平,抑制Smad2信号。结论:粉防甲素抑制scf中Smad2信号和纤维化反应,与Smad7上调有关,提示其在预防小梁切除术后结膜过度瘢痕/纤维化或严重结膜炎症患者中的潜在治疗价值。
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.