PMID- 25872526
OWN - NLM
STAT- MEDLINE
DCOM- 20160125
LR  - 20150504
IS  - 1791-244X (Electronic)
IS  - 1107-3756 (Linking)
VI  - 35
IP  - 6
DP  - 2015 Jun
TI  - Effect of zinc on high glucose-induced epithelial-to-mesenchymal transition in 
      renal tubular epithelial cells.
PG  - 1747-54
LID - 10.3892/ijmm.2015.2170 [doi]
AB  - 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 immuno fl uorescence 
      staining and western blot analysis. The present study identified that 10 microM of Zn 
      supplementation prevented EMT changes, such as the loss of E-cadherin and the 
      increase in alpha-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 microM Zn 
      supplementation inhibited HG-induced transforming growth factor-beta1 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.
FAU - Zhang, Xiuli
AU  - Zhang X
AD  - Department of Pathophysiology, China Medical University, Shenyang, Liaoning 
      110001, P.R. China.
FAU - Liang, Dan
AU  - Liang D
AD  - Troops of 95935 Unit, Harbin, Heilongjiang 150111, P.R. China.
FAU - Chi, Zhi-Hong
AU  - Chi ZH
AD  - Department of Pathophysiology, China Medical University, Shenyang, Liaoning 
      110001, P.R. China.
FAU - Chu, Qingqing
AU  - Chu Q
AD  - Department of Pathophysiology, China Medical University, Shenyang, Liaoning 
      110001, P.R. China.
FAU - Zhao, Chenghai
AU  - Zhao C
AD  - Department of Pathophysiology, China Medical University, Shenyang, Liaoning 
      110001, P.R. China.
FAU - Ma, Rong-Zheng
AU  - Ma RZ
AD  - Department of Pathophysiology, China Medical University, Shenyang, Liaoning 
      110001, P.R. China.
FAU - Zhao, Yue
AU  - Zhao Y
AD  - Key Laboratory of Medical Cell Biology, Ministry of Education, China Medical 
      University, Shenyang, Liaoning 110001, P.R. China.
FAU - Li, Hongjuan
AU  - Li H
AD  - Troops of 95935 Unit, Harbin, Heilongjiang 150111, P.R. China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150407
PL  - Greece
TA  - Int J Mol Med
JT  - International journal of molecular medicine
JID - 9810955
RN  - EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
RN  - IY9XDZ35W2 (Glucose)
RN  - J41CSQ7QDS (Zinc)
SB  - IM
MH  - Animals
MH  - Cell Line
MH  - Epithelial Cells/*metabolism
MH  - Epithelial-Mesenchymal Transition/*drug effects
MH  - Glucose/metabolism/*pharmacology
MH  - Kidney Tubules, Proximal/*metabolism
MH  - MAP Kinase Signaling System/*drug effects
MH  - Phosphatidylinositol 3-Kinases/metabolism
MH  - Rats
MH  - Zinc/metabolism/*pharmacology
MH  - p38 Mitogen-Activated Protein Kinases/metabolism
EDAT- 2015/04/16 06:00
MHDA- 2016/01/26 06:00
CRDT- 2015/04/16 06:00
PHST- 2014/11/24 00:00 [received]
PHST- 2015/03/23 00:00 [accepted]
PHST- 2015/04/16 06:00 [entrez]
PHST- 2015/04/16 06:00 [pubmed]
PHST- 2016/01/26 06:00 [medline]
AID - 10.3892/ijmm.2015.2170 [doi]
PST - ppublish
SO  - Int J Mol Med. 2015 Jun;35(6):1747-54. doi: 10.3892/ijmm.2015.2170. Epub 2015 Apr 
      7.