Journal article
GSTA3 Attenuates Renal Interstitial Fibrosis by Inhibiting TGF-Beta-Induced Tubular Epithelial-Mesenchymal Transition and Fibronectin Expression
PloS one, Vol.11(9), e0160855
2016
DOI: 10.1371/journal.pone.0160855
PMCID: PMC5014405
PMID: 27602565
Abstract
Tubular epithelial-mesenchymal transition (EMT) has been widely accepted as the underlying mechanisms of renal interstitial fibrosis (RIF). The production of reactive oxygen species (ROS) plays a vital role in tubular EMT process. The purpose of this study was to investigate the involved molecular mechanisms in TGF-beta-induced EMT and identify the potential role of glutathione S-transferase alpha 3 (GSTA3) in this process. The iTRAQ screening was performed to identify protein alterations of the rats underwent unilateral-ureteral obstruction (UUO). Protein expression of GSTA3 in patients with obstructive nephropathy and UUO rats was detected by immunohistochemistry. Protein and mRNA expression of GSTA3 in UUO rats and NRK-52E cells were determined by Western blot and RT-PCR. siRNA and overexpression plasmid were transfected specifically to assess the role of GSTA3 in RIF. The generation of ROS was measured by dichlorofluorescein fluorescence analysis. GSTA3 protein and mRNA expression was significantly reduced in UUO rats. Immunohistochemical analysis revealed that GSTA3 expression was reduced in renal cortex in UUO rats and patients with obstructive nephropathy. Treating with TGF-β1 down-regulated GSTA3 expression in NRK-52E cells, which have been found to be correlated with the decreased expression in E-cadherin and megalin and increased expression in α-smooth muscle actin. Furthermore, knocking down GSTA3 in NRK-52 cells led to increased production of ROS and tubular EMT, whereas overexpressing GSTA3 ameliorated ROS production and prevented the occurrence of tubular EMT. GSTA3 plays a protective role against tubular EMT in renal fibrosis, suggesting GSTA3 is a potential therapeutic target for RIF.
Details
- Title: Subtitle
- GSTA3 Attenuates Renal Interstitial Fibrosis by Inhibiting TGF-Beta-Induced Tubular Epithelial-Mesenchymal Transition and Fibronectin Expression
- Creators
- Yun Xiao - Division of Nephrology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China, 510120Jishi Liu - Division of Nephrology, Xiangya Hospital, Central South University, Changsha, China, 410078Yu Peng - Division of Nephrology, Xiangya Hospital, Central South University, Changsha, China, 410078Xuan Xiong - Division of Nephrology, Xiangya Hospital, Central South University, Changsha, China, 410078Ling Huang - Division of Nephrology, Xiangya Hospital, Central South University, Changsha, China, 410078Huixiang Yang - Division of Digestive Medicine, Xiangya Hospital, Central South University, Changsha, China, 410078Jian Zhang - Department of Microbial Infection and Immunity, The Ohio State University, Columbus, Ohio, United States of AmericaLijian Tao - State Key Laboratory of Medical Genetics of China, Central South University, Changsha, China, 410078
- Resource Type
- Journal article
- Publication Details
- PloS one, Vol.11(9), e0160855
- DOI
- 10.1371/journal.pone.0160855
- PMID
- 27602565
- PMCID
- PMC5014405
- NLM abbreviation
- PLoS One
- ISSN
- 1932-6203
- eISSN
- 1932-6203
- Publisher
- Public Library of Science; United States
- Grant note
- name: National Natural Science Foundation of China (CN), award: 81370547; name: CHINA-CANADA Joint Health Research Initiative Foundation, award: 81061120524/H07
- Language
- English
- Date published
- 2016
- Academic Unit
- Pathology
- Record Identifier
- 9984047657302771
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