Effect of zinc on high glucose-induced epithelial-to-mesenchymal transition in renal tubular epithelial cells

Zhang,Xiuli; Liang,Dan; Chi,Zhi-Hong; Chu,Qingqing; Zhao,Chenghai; Ma,Rong-Zheng; Zhao,Yue; Li,Hongjuan

doi:10.3892/ijmm.2015.2170

Effect of zinc on high glucose-induced epithelial-to-mesenchymal transition in renal tubular epithelial cells

Authors:
- Xiuli Zhang
- Dan Liang
- Zhi-Hong Chi
- Qingqing Chu
- Chenghai Zhao
- Rong-Zheng Ma
- Yue Zhao
- Hongjuan Li
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Affiliations: Department of Pathophysiology, China Medical University, Shenyang, Liaoning 110001, P.R. China, Troops of 95935 Unit, Harbin, Heilongjiang 150111, P.R. China, Key Laboratory of Medical Cell Biology, Ministry of Education, China Medical University, Shenyang, Liaoning 110001, P.R. China
Published online on: April 7, 2015 https://doi.org/10.3892/ijmm.2015.2170
Pages: 1747-1754

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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.

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