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A. Kitano, O. Yamanaka, S. Saika, K. Ikeda, Y. Okada, K. Shirai, Y. Ohnishi; Effect of Tetrandrine on Fibrogenic Behaviors of Cultured Human Subconjunctival Fibroblasts. Invest. Ophthalmol. Vis. Sci. 2007;48(13):4280.
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To examine the effect of tetrandrine on fibrogenic behaviors of cultured human subconjunctival fibroblasts (hSCFs). Tetrandrine is a bioactive constituent of an herbal medicine.
Confluent cultures of hSCFs were treated with tetrandrine (0 - 5.0 micro g/ml). Its effects on expression of a-smooth muscle actin, collagen I and III, and fibronectin were investigated by using immunocytochemistry, western blotting, enzyme-immunoassay or real-time RT-PCR. Tetrandrin's effect on cell migration or proliferation was determined by in vitro wound closure model in a cell monolayer or by Alamar blue assay, respectively. Effect of tetrandrine on Smad2 phosphorylation and Smad7 expression was examined by immunocytochemistry and western blotting.
Adding tetrandrine suppressed expression of collagens and fibronectin at mRNA or protein level and cell migration, but not cell proliferation. Treatment of cells with tetrandrine up-regulated expression of Smad7, an inhibitory Smad, and reduced nuclear translocation of phospho-Smad2 in cells. Control cells showed a peak of Smad2 acticvation at 0.5 hr.
Tetrandrine inhibits fibrogenic behaviors of cultured hSCFs. The mechanism of action might include that this compound induce Smad7 that resulted in supprssion of Smad2 signal.
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