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

Authors Liu X, Zhang X, Cai X, Dong J, Chi Y, Chi Z, Gu HF

Received 21 December 2020

Accepted for publication 3 February 2021

Published 2 March 2021 Volume 2021:14 Pages 929—940

DOI https://doi.org/10.2147/DMSO.S296990

Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 2

Editor who approved publication: Dr Antonio Brunetti


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 China

Correspondence: Xiuli Zhang
Department of Nephrology, Second People’s Hospital, The First Affiliated Hospital of Shenzhen University, Shenzhen, Guangdong Province, 518000, People’s Republic of China
Email [email protected]
Harvest F Gu
Center for Pathophysiology, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, Jiangsu Province, 210009, People’s Republic of China
Email [email protected]

Objective: 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

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