Arecoline, a component of betel nuts, is a known carcinogen that causes oral cancers among those who chew betel nuts. Betel nut chewing is also associated with an increased risk of chronic kidney disease (CKD), but the role of arecoline in this association is unclear. This in vitro study investigates the effects of arecoline on cultured human kidney (HK2) cells. We observed that arecoline had no effect on cell viability but increased cell migration in a dose-dependent manner. Western blot analysis showed that arecoline treatment caused a dose-dependent decrease in E-cadherin expression and dose-dependent increases in N-cadherin, vimentin, α-SMA, and collagen expression; reverse transcriptase-polymerase chain reaction analysis revealed dose-dependent increases in α-SMA and collagen mRNA. Arecoline treatment upregulated the expression of phosphorylated extracellular signal-regulated kinase through epithelial mesenchymal transition and renal fibrosis in HK2 cells. These findings demonstrate that arecoline plays a role in inducing the epithelial mesenchymal transition and fibrogenesis in renal tubule cells and suggest that arecoline promotes the progression of CKD.

中文翻译：

---

槟榔碱通过上调 ERK 介导的信号通路诱导 HK2 细胞上皮间充质转化

槟榔的一种成分槟榔碱是一种已知的致癌物质，会导致咀嚼槟榔的人患上口腔癌。嚼槟榔也与慢性肾病 (CKD) 风险增加有关，但槟榔碱在这种关联中的作用尚不清楚。这项体外研究调查了槟榔碱对培养的人肾 (HK2) 细胞的影响。我们观察到槟榔碱对细胞活力没有影响，但以剂量依赖性方式增加细胞迁移。蛋白质印迹分析显示，槟榔碱处理导致 E-cadherin 表达呈剂量依赖性降低，N-cadherin、波形蛋白、α-SMA 和胶原蛋白表达呈剂量依赖性增加；逆转录酶-聚合酶链反应分析显示 α-SMA 和胶原 mRNA 呈剂量依赖性增加。槟榔碱处理通过 HK2 细胞中的上皮间充质转化和肾纤维化上调磷酸化细胞外信号调节激酶的表达。这些发现表明，槟榔碱在诱导肾小管细胞上皮间质转化和纤维化中起作用，并表明槟榔碱促进了 CKD 的进展。