title: Effect of zinc on high glucose-induced epithelial-to-mesenchymal transition in renal tubular epithelial cells.
abstract: Zinc (Zn) as an essential dietary element has been indicated in a number of protein functions in the prevention of numerous types of epithelial-to-mesenchymal transition (EMT)-driven fibrosis in vivo. However, relatively little is known regarding its effect in the EMT of the renal tubular epithelial cells, which play an important role in renal tubulointerstitial fibrosis and is an important component of the renal injury that is associated with diabetic nephropathy. The present study investigated the effect of Zn on the high glucose (HG)-induced EMT in a normal rat kidney tubular epithelial cell line (NRK-52E cells) and the underlying molecular mechanisms by immunoﬂuorescence staining and western blot analysis. The present study identified that 10 µM of Zn supplementation prevented EMT changes, such as the loss of E-cadherin and the increase in α-smooth muscle actin and vimentin expression. Conversely, depletion of Zn with N,N,N',N'-tetrakis (2-pyridylmethyl)ethylenediamine in these cells aggravated changes in HG-induced EMT markers. Additionally, 10 µM Zn supplementation inhibited HG-induced transforming growth factor-β1 overexpression and reactive oxygen species production. Of note, HG increased phosphatidylinositol 3-kinase/Akt (PI3K/Akt) and mitogen-activated protein kinase (MAPK) pathways activation and Zn reversed HG-induced expression of PI3K/Akt, extracellular-signal-regulated kinase (ERK) and p38 MAPK, as well as EMT proteins. Finally, inhibitors of PI3K/Akt, ERK and p38 MAPK, and Zn supplementation blocked the HG-induced EMT in NRK-52E cells. These results indicate that physiologically optimal levels of Zn can inhibit HG-induced EMT of the NRK-52E cells possibly through several mechanisms, including abrogation of HG-induced oxidative stress, and PI3K/Akt, p38 MAPK and ERK activation in NRK-52E cells.
authors: Department of Pathophysiology, China Medical University, Shenyang, Liaoning 110001, P.R. China.
authors: Xiuli
authors: X
authors: Zhang
authors: Troops of 95935 Unit, Harbin, Heilongjiang 150111, P.R. China.
authors: Dan
authors: D
authors: Liang
authors: Department of Pathophysiology, China Medical University, Shenyang, Liaoning 110001, P.R. China.
authors: Zhi-Hong
authors: ZH
authors: Chi
authors: Department of Pathophysiology, China Medical University, Shenyang, Liaoning 110001, P.R. China.
authors: Qingqing
authors: Q
authors: Chu
authors: Department of Pathophysiology, China Medical University, Shenyang, Liaoning 110001, P.R. China.
authors: Chenghai
authors: C
authors: Zhao
authors: Department of Pathophysiology, China Medical University, Shenyang, Liaoning 110001, P.R. China.
authors: Rong-Zheng
authors: RZ
authors: Ma
authors: Key Laboratory of Medical Cell Biology, Ministry of Education, China Medical University, Shenyang, Liaoning 110001, P.R. China.
authors: Yue
authors: Y
authors: Zhao
authors: Troops of 95935 Unit, Harbin, Heilongjiang 150111, P.R. China.
authors: Hongjuan
authors: H
authors: Li
mesh_terms: D000818:Animals; D002460:Cell Line; D004847:Epithelial Cells / Q000378:metabolism*; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects*; D005947:Glucose / Q000378:metabolism / Q000494:pharmacology*; D007687:Kidney Tubules, Proximal / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051381:Rats; D015032:Zinc / Q000378:metabolism / Q000494:pharmacology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D019869:Phosphatidylinositol 3-Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D005947:Glucose; D015032:Zinc