Effects of Curcumin on High Glucose-Induced Epithelial-to-Mesenchymal Transition in Renal Tubular Epithelial Cells Through the TLR4-NF-κB Signaling Pathway

Xinhui Liu,1 Xiuli Zhang,2,3 Xiaoyi Cai,2 Jiqiu Dong,2 Yinmao Chi,4 Zhihong Chi,3 Harvest F Gu5 1Traditional Chinese Medicine, Liaoning University of Traditional Chinese Medicine, Shenyang, Liaoning Province, 110847, People’s Republic of China; 2Department of Nephrology, Second People&...

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Autores principales: Liu X, Zhang X, Cai X, Dong J, Chi Y, Chi Z, Gu HF
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Publicado: Dove Medical Press 2021
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spelling oai:doaj.org-article:ca8a8851885e4a12bba817e6ef062a382021-12-02T13:33:14ZEffects of Curcumin on High Glucose-Induced Epithelial-to-Mesenchymal Transition in Renal Tubular Epithelial Cells Through the TLR4-NF-κB Signaling Pathway1178-7007https://doaj.org/article/ca8a8851885e4a12bba817e6ef062a382021-03-01T00:00:00Zhttps://www.dovepress.com/effects-of-curcumin-on-high-glucose-induced-epithelial-to-mesenchymal--peer-reviewed-article-DMSOhttps://doaj.org/toc/1178-7007Xinhui Liu,1 Xiuli Zhang,2,3 Xiaoyi Cai,2 Jiqiu Dong,2 Yinmao Chi,4 Zhihong Chi,3 Harvest F Gu5 1Traditional Chinese Medicine, Liaoning University of Traditional Chinese Medicine, Shenyang, Liaoning Province, 110847, People’s Republic of China; 2Department of Nephrology, Second People’s Hospital, The First Affiliated Hospital of Shenzhen University, Shenzhen, Guangdong Province, 518000, People’s Republic of China; 3Department of Pathophysiology, China Medical University, Shenyang, Liaoning Province, 110001, People’s Republic of China; 4Department of Physiology, China Medical University, Shenyang, Liaoning Province, 110001, People’s Republic of China; 5Center for Pathophysiology, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, Jiangsu Province, 210009, People’s Republic of ChinaCorrespondence: Xiuli ZhangDepartment of Nephrology, Second People’s Hospital, The First Affiliated Hospital of Shenzhen University, Shenzhen, Guangdong Province, 518000, People’s Republic of ChinaEmail zhangxiuli54321@sina.comHarvest F GuCenter for Pathophysiology, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, Jiangsu Province, 210009, People’s Republic of ChinaEmail feng.gu@cpu.edu.cnObjective: Diabetic kidney disease (DKD) is a microvascular complication in diabetes mellitus, while tubuloepithelial to mesenchymal transition (EMT) of mature tubular epithelial cells is a key point in the early development and progression of renal interstitial fibrosis. The present study aimed to investigate the protective effects of Curcumin on EMT and fibrosis in cultured normal rat kidney tubular epithelial cell line (NRK-52E).Methods: By using immunofluorescence staining and Western blot protocols, in vitro experiments were designed to analyze EMT markers, including collagen I and E-cadherin in high glucose (HG) exposed NRK-52E cells and to detect the expression levels of phosphorylated-NF-κB, TLR4 and reactive oxygen species (ROS) after Curcumin pre-treatment. With co-treatment with TAK242, these molecules in the TLR4-NF-κB signaling pathway were further evaluated.Results: Curcumin decreased the HG-induced EMT levels and ROS production in NRK-52E cells. Furthermore, Curcumin was found to inhibit the TLR4-NF-κB signaling activation in HG-induced EMT of NRK-52E cells.Conclusion: The present study provides evidence suggesting a novel mechanism that Curcumin exerts the anti-fibrosis effects via inhibiting activation of the TLR4-NF-κB signal pathway and consequently protecting the HG-induced EMT in renal tubular epithelial cells. Thereby, TLR4-NF-κB may be a useful target for therapeutic intervention in DKD.Keywords: diabetic kidney disease, tubuloepithelial to mesenchymal transition, toll-like receptor 4, curcumin, inflammationLiu XZhang XCai XDong JChi YChi ZGu HFDove Medical Pressarticlediabetic kidney diseasetubuloepithelial to mesenchymal transitiontoll-like receptor 4curcumininflammationSpecialties of internal medicineRC581-951ENDiabetes, Metabolic Syndrome and Obesity: Targets and Therapy, Vol Volume 14, Pp 929-940 (2021)
institution DOAJ
collection DOAJ
language EN
topic diabetic kidney disease
tubuloepithelial to mesenchymal transition
toll-like receptor 4
curcumin
inflammation
Specialties of internal medicine
RC581-951
spellingShingle diabetic kidney disease
tubuloepithelial to mesenchymal transition
toll-like receptor 4
curcumin
inflammation
Specialties of internal medicine
RC581-951
Liu X
Zhang X
Cai X
Dong J
Chi Y
Chi Z
Gu HF
Effects of Curcumin on High Glucose-Induced Epithelial-to-Mesenchymal Transition in Renal Tubular Epithelial Cells Through the TLR4-NF-κB Signaling Pathway
description Xinhui Liu,1 Xiuli Zhang,2,3 Xiaoyi Cai,2 Jiqiu Dong,2 Yinmao Chi,4 Zhihong Chi,3 Harvest F Gu5 1Traditional Chinese Medicine, Liaoning University of Traditional Chinese Medicine, Shenyang, Liaoning Province, 110847, People’s Republic of China; 2Department of Nephrology, Second People’s Hospital, The First Affiliated Hospital of Shenzhen University, Shenzhen, Guangdong Province, 518000, People’s Republic of China; 3Department of Pathophysiology, China Medical University, Shenyang, Liaoning Province, 110001, People’s Republic of China; 4Department of Physiology, China Medical University, Shenyang, Liaoning Province, 110001, People’s Republic of China; 5Center for Pathophysiology, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, Jiangsu Province, 210009, People’s Republic of ChinaCorrespondence: Xiuli ZhangDepartment of Nephrology, Second People’s Hospital, The First Affiliated Hospital of Shenzhen University, Shenzhen, Guangdong Province, 518000, People’s Republic of ChinaEmail zhangxiuli54321@sina.comHarvest F GuCenter for Pathophysiology, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, Jiangsu Province, 210009, People’s Republic of ChinaEmail feng.gu@cpu.edu.cnObjective: Diabetic kidney disease (DKD) is a microvascular complication in diabetes mellitus, while tubuloepithelial to mesenchymal transition (EMT) of mature tubular epithelial cells is a key point in the early development and progression of renal interstitial fibrosis. The present study aimed to investigate the protective effects of Curcumin on EMT and fibrosis in cultured normal rat kidney tubular epithelial cell line (NRK-52E).Methods: By using immunofluorescence staining and Western blot protocols, in vitro experiments were designed to analyze EMT markers, including collagen I and E-cadherin in high glucose (HG) exposed NRK-52E cells and to detect the expression levels of phosphorylated-NF-κB, TLR4 and reactive oxygen species (ROS) after Curcumin pre-treatment. With co-treatment with TAK242, these molecules in the TLR4-NF-κB signaling pathway were further evaluated.Results: Curcumin decreased the HG-induced EMT levels and ROS production in NRK-52E cells. Furthermore, Curcumin was found to inhibit the TLR4-NF-κB signaling activation in HG-induced EMT of NRK-52E cells.Conclusion: The present study provides evidence suggesting a novel mechanism that Curcumin exerts the anti-fibrosis effects via inhibiting activation of the TLR4-NF-κB signal pathway and consequently protecting the HG-induced EMT in renal tubular epithelial cells. Thereby, TLR4-NF-κB may be a useful target for therapeutic intervention in DKD.Keywords: diabetic kidney disease, tubuloepithelial to mesenchymal transition, toll-like receptor 4, curcumin, inflammation
format article
author Liu X
Zhang X
Cai X
Dong J
Chi Y
Chi Z
Gu HF
author_facet Liu X
Zhang X
Cai X
Dong J
Chi Y
Chi Z
Gu HF
author_sort Liu X
title Effects of Curcumin on High Glucose-Induced Epithelial-to-Mesenchymal Transition in Renal Tubular Epithelial Cells Through the TLR4-NF-κB Signaling Pathway
title_short Effects of Curcumin on High Glucose-Induced Epithelial-to-Mesenchymal Transition in Renal Tubular Epithelial Cells Through the TLR4-NF-κB Signaling Pathway
title_full Effects of Curcumin on High Glucose-Induced Epithelial-to-Mesenchymal Transition in Renal Tubular Epithelial Cells Through the TLR4-NF-κB Signaling Pathway
title_fullStr Effects of Curcumin on High Glucose-Induced Epithelial-to-Mesenchymal Transition in Renal Tubular Epithelial Cells Through the TLR4-NF-κB Signaling Pathway
title_full_unstemmed Effects of Curcumin on High Glucose-Induced Epithelial-to-Mesenchymal Transition in Renal Tubular Epithelial Cells Through the TLR4-NF-κB Signaling Pathway
title_sort effects of curcumin on high glucose-induced epithelial-to-mesenchymal transition in renal tubular epithelial cells through the tlr4-nf-κb signaling pathway
publisher Dove Medical Press
publishDate 2021
url https://doaj.org/article/ca8a8851885e4a12bba817e6ef062a38
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