title: Curcumin protects renal tubular epithelial cells from high glucose-induced epithelial-to-mesenchymal transition through Nrf2-mediated upregulation of heme oxygenase-1.
abstract: Curcumin has been observed to exhibit an anti-fibrotic effect in the liver, lung and gallbladder. However, the mechanisms underlying the cytoprotective effects of curcumin remain to be elucidated. The epithelial-to-mesenchymal transition (EMT) of mature tubular epithelial cells in the kidney is considered to contribute to the renal accumulation of matrix proteins associated with diabetic nephropathy. The EMT is also closely associated with the progression of renal interstitial fibrosis and oxidative stress. This process may occur through abrogation of high glucose (HG)-induced oxidative stress via activation of nuclear factor (erythroid-derived 2)-like 2 (Nrf2) and heme oxygenase-1 (HO-1) in kidney tubular epithelial cells. In the present study, the effect of curcumin on HG-induced EMT in the NRK-52E normal rat kidney tubular epithelial cell line was investigated, and whether the effect of curcumin was mediated by the induction of Nrf2 and HO-1 expression was examined. The present study revealed that curcumin was able to prevent events associated with EMT, including the downregulation of E-cadherin and the increased expression of α-smooth muscle actin. Further analysis revealed that the expression levels of Nrf2 and HO-1 protein were elevated to a greater extent in the curcumin pretreated NRK-52E cells compared with those of the control. Notably, knockdown of Nrf2 with small interfering RNA prevented the curcumin-induced elevation in expression of HO-1 and the associated anti-fibrotic effects. In conclusion, the present findings suggested that curcumin may be significant in cellular antioxidant defense, through the activation of Nrf2 and HO-1, thereby protecting the NRK-52E cells from HG-induced EMT.
authors.affiliation: Department of Nephrology, Benxi Center Hospital, China Medical University, Benxi, Liaoning 117000, P.R. China.
authors.forename: Xiuli
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Troops of 95935 Unit, Harbin, Heilongjiang 150111, P.R. China.
authors.forename: Dan
authors.initials: D
authors.lastname: Liang
authors.affiliation: Troops of 93253 Unit, Harbin, Heilongjiang 150111, P.R. China.
authors.forename: Lin
authors.initials: L
authors.lastname: Guo
authors.affiliation: Department of Nephrology, Benxi Center Hospital, China Medical University, Benxi, Liaoning 117000, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Liang
authors.affiliation: Department of Nephrology, Benxi Center Hospital, China Medical University, Benxi, Liaoning 117000, P.R. China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: Troops of 95935 Unit, Harbin, Heilongjiang 150111, P.R. China.
authors.forename: Hongjuan
authors.initials: H
authors.lastname: Li
authors.affiliation: Key Laboratory of Medical Cell Biology, Ministry of Education, China Medical University, Shenyang, Liaoning 110001, P.R. China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of Nephrology, Benxi Center Hospital, China Medical University, Benxi, Liaoning 117000, P.R. China.
authors.forename: Shumin
authors.initials: S
authors.lastname: Lu
authors.affiliation: Department of Pathophysiology, China Medical University, Shenyang, Liaoning 110001, P.R. China.
authors.forename: Zhi-Hong
authors.initials: ZH
authors.lastname: Chi
mesh_terms: D000818:Animals; D003474:Curcumin / Q000008:administration & dosage*; D003928:Diabetic Nephropathies / Q000378:metabolism* / Q000473:pathology; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects; D005947:Glucose / Q000378:metabolism; D006419:Heme Oxygenase (Decyclizing) / Q000096:biosynthesis* / Q000378:metabolism; D006801:Humans; D007684:Kidney Tubules / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D051267:NF-E2-Related Factor 2 / Q000096:biosynthesis* / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D051267:NF-E2-Related Factor 2; C495637:Nfe2l2 protein, rat; D006419:Heme Oxygenase (Decyclizing); C491523:Hmox1 protein, rat; D003474:Curcumin; D005947:Glucose