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Arecoline induces epithelial mesenchymal transition in HK2 cells by upregulating the ERK ‐mediated signaling pathway
Author(s) -
Hsieh YiHsien,
Syu RuJiang,
Lee ChuChe,
Lin ShinHuey,
Lee ChienHsing,
Cheng ChunWen,
Tsai JenPi
Publication year - 2020
Publication title -
environmental toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.813
H-Index - 77
eISSN - 1522-7278
pISSN - 1520-4081
DOI - 10.1002/tox.22937
Subject(s) - arecoline , epithelial–mesenchymal transition , cancer research , chemistry , cell growth , downregulation and upregulation , betel , biology , endocrinology , microbiology and biotechnology , biochemistry , receptor , muscarinic acetylcholine receptor , structural engineering , nut , engineering , gene
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.