1,25(OH)(2) D-3 attenuates indoxyl sulfate-induced epithelial-to-mesenchymal cell transition via inactivation of PI3K/Akt/beta-catenin signaling in renal tubular epithelial cells

doi:10.1016/j.nut.2019.110554

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題名:	1,25(OH)(2) D-3 attenuates indoxyl sulfate-induced epithelial-to-mesenchymal cell transition via inactivation of PI3K/Akt/beta-catenin signaling in renal tubular epithelial cells
作者:	Chang, LC;Sun, HL;Tsai, CH;Kuo, CW;Liu, KL;Lii, CK;Huang, CS;Li, CC
關鍵詞:	1,25(OH)2 D-3;beta-catenin;EMT;HK-2 cells;Indoxyl sulfate
日期:	2020
上傳時間:	2022-08-09T08:06:25Z (UTC)
出版者:	ELSEVIER SCIENCE INC
ISSN:	0899-9007
摘要:	Objectives: Indoxyl sulfate (IS), a uremic toxin, has been shown to promote the epithelial-to-mesenchymal transition (EMT) of human proximal tubular cells and to accelerate the progression of chronic kidney disease (CKD). Despite the well-known protective role of 1,25-dihydroxyvitamin D-3 [1,25(OH)(2) D-3] in EMT, the effect of 1,25(OH)(2) D-3 on IS-induced EMT in human proximal tubular epithelial cells and the underlying mechanism remain unclear. The aim of this study was to determine whether IS (0-1 mM) dose-dependently inhibited the protein expression of E-cadherin and increased the protein expression of alpha-smooth muscle actin, N-cadherin, and fibronectin. Methods: This study investigated the molecular mechanism by which 1,25(OH)(2) D-3 attenuates IS-induced EMT. HK-2 human renal tubular epithelial cells was used as the study model, and the MTT assay, Western Blotting, siRNA knockdown technique were used to explore the effects of 1,25(OH)(2) D-3 on EMT in the presence of IS. Results: Pretreatment with 1,25(OH)(2) D-3 inhibited the IS-induced EMT-associated protein expression in HK-2 cells. IS induced the phosphorylation of Akt (5473) and beta-catenin (S552) and subsequently increased the nuclear accumulation of P-catenin. Pretreatment with 1,25(OH)(2) D-3 and LY294002 (phosphoinositide 3-kinase [PIK3] inhibitor) significantly inhibited the IS-induced phosphorylation of Akt and beta-catenin, nuclear p-catenin accumulation, and EMT-associated protein expression. Conclusions: Results from the present study revealed that the anti-EMT effect of 1,25(OH)(2) D-3 is likely through inhibition of the PI3K/Akt/beta-catenin pathway, which leads to down-regulation of IS-driven EMT-associated protein expression in HK-2 human renal tubular epithelial cells. (C) 2019 Elsevier Inc. All rights reserved.
URI:	http://dx.doi.org/10.1016/j.nut.2019.110554 https://www.webofscience.com/wos/woscc/full-record/WOS:000502883900005 https://ir.csmu.edu.tw:8080/handle/310902500/24689
關聯:	NUTRITION ,2020 ,v69
顯示於類別:	[中山醫學大學研究成果] 期刊論文

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