Epigallocatechin-3-gallate attenuates arsenic-induced fibrogenic changes in human kidney epithelial cells through reversal of epigenetic aberrations and antioxidant activities.
Epigallocatechin-3-gallate attenuates arsenic-induced fibrogenic changes in human kidney epithelial cells through reversal of epigenetic aberrations and antioxidant activities.
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DOI：
10.1002/biof.2027
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发表时间：
2023-12
期刊：
影响因子：
6
通讯作者：
Mary Sonia Iheanacho;Ramji Kandel;Pritimadhab Roy;Kamaleshwar P. Singh
中科院分区：
文献类型：
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作者：
Mary Sonia Iheanacho;Ramji Kandel;Pritimadhab Roy;Kamaleshwar P. Singh
肾纤维化是慢性肾脏疾病（CKD）的中间致病阶段。包括砷在内的肾毒物可通过诱导氧化应激和表观遗传畸变引起肾纤维化。表没食子儿茶素- 3 -没食子酸酯（EGCG）是一种绿茶多酚，已知具有抗氧化和表观遗传调节特性。EGCG是否可以通过其抗氧化和表观遗传调节活性来减弱纤维形成尚不清楚。因此，本研究的目的是确定EGCG是否可以减轻砷诱导的肾上皮细胞急性损伤和长期暴露相关的纤维化。为了解决这个问题，我们用EGCG处理了两种急性和长期暴露于砷的人肾上皮细胞系Caki‐1和HK‐2。通过测量细胞生长、活性氧（ROS）产生、基因表达和组蛋白标记的表观遗传变化来评估EGCG对砷诱导的细胞毒性和纤维原性的保护作用。结果表明，EGCG对砷诱导的急性细胞毒性具有保护作用。EGCG清除砷暴露细胞中增加的活性氧水平。EGCG可恢复砷暴露细胞中纤维化基因的异常表达。砷诱导的纤维化改变的消除也与EGCG介导的砷诱导的表观遗传调控蛋白和组蛋白标记异常表达的恢复有关。本研究的新发现表明，EGCG通过其抗氧化和表观遗传调节能力，对砷诱导的肾上皮细胞毒性和纤维化改变具有保护作用。
Renal fibrosis is a pathogenic intermediate stage of chronic kidney disease (CKD). Nephrotoxicants including arsenic can cause kidney fibrosis through induction of oxidative stress and epigenetic aberrations. Epigallocatechin‐3‐gallate (EGCG), a green tea polyphenol, is known to have antioxidant and epigenetic modulation properties. Whether EGCG, through its antioxidant and epigenetic modulating activities, can attenuate fibrogenesis is not known. Therefore, the objective of this study was to determine whether EGCG can attenuate arsenic‐induced acute injury and long‐term exposure associated fibrogenicity in kidney epithelial cells. To address this question, two human kidney epithelial cell lines Caki‐1 and HK‐2 exposed to arsenic for both acute and long‐term durations were treated with EGCG. The protective effect of EGCG on arsenic‐induced cytotoxicity and fibrogenicity were evaluated by measuring the cell growth, reactive oxygen species (ROS) production, genes expression, and epigenetic changes in histone marks. Results revealed that EGCG has a protective effect in arsenic‐induced acute cytotoxicity in these cells. EGCG scavenges the increased levels of ROS in arsenic exposed cells. Aberrant expression of fibrogenic genes in arsenic exposed cells were restored by EGCG. Abrogation of arsenic‐induced fibrogenic changes was also associated with EGCG‐mediated restoration of arsenic‐induced aberrant expression of epigenetic regulatory proteins and histone marks. Novel findings of this study suggest that EGCG, through its antioxidant and epigenetic modulation capacities, has protective effects against arsenic‐induced cytotoxicity and fibrogenic changes in kidney epithelial cells.