上皮-间质转换
波形蛋白
连环素
小干扰RNA
纤维连接蛋白
间充质干细胞
化学
细胞外基质
细胞生物学
成纤维细胞
信号转导
癌症研究
基因敲除
分子生物学
转染
生物
下调和上调
生物化学
免疫学
Wnt信号通路
细胞凋亡
免疫组织化学
基因
体外
作者
Rattiyaporn Kanlaya,Paleerath Peerapen,Angkhana Nilnumkhum,Sirikanya Plumworasawat,Kanyarat Sueksakit,Visith Thongboonkerd
标识
DOI:10.1016/j.jnutbio.2019.108266
摘要
Several lines of evidence have demonstrated anti-fibrotic property of epigallocatechin-3-gallate (EGCG) in many tissues/organs but with unclear mechanisms. This study thus aimed to define cellular mechanisms underlying such protective effect of EGCG. HK-2 renal cells were treated with 5 ng/ml TGF-β1 for 24 h with/without pretreatment by 5 μM EGCG for 1 h. The cells were then evaluated by morphological examination, immunofluorescence study, semi-quantitative RT-PCR, Western blotting, and atomic force microscopy (AFM). The results showed that TGF-β1-treated cells underwent epithelial mesenchymal transition (EMT) as evidenced by morphological change into fibroblast-like and increases in spindle index, mesenchymal markers (Snail1 and vimentin), extracellular matrix (fibronectin), cell stiffness (by AFM measurement) and actin stress fibers, whereas the epithelial markers (E-cadherin and ZO-1) were decreased. All of these features were abolished by EGCG pretreatment. Functional studies revealed that the anti-fibrotic property of EGCG was, at least in part, due to de-activation/stabilization of GSK-3β/β-catenin/Snail1 (EMT-triggering) signaling pathway that was activated by TGF-β1 as shown by maintaining phosphorylated GSK-3β, β-catenin and Snail1 to their basal levels. Additionally, Nrf2 knockdown by small interfering RNA could abolish the EGCG effect on β-catenin expression. These data indicate that EGCG attenuates TGF-β1-induced EMT in renal tubular cells through GSK-3β/β-catenin/Snail1 and Nrf2 pathways.
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