The Protective Role of Nrf2 in Renal Tubular Cells in Oxidised Low-Density Lipoprotein-Induced Fibrosis.

Abstract

Background: CD36 is the receptor of oxidised low-density lipoprotein (OxLDL) in renal tubular epithelial cells. Nuclear factor erythroid 2-related factor 2 (Nrf2) is the key factor in the activation of the Nrf2 signalling pathway and the regulation of oxidative stress. Kelch-like ECH-associated protein 1 (Keap1) is known as an Nrf2 inhibitor. Methods: We used OxLDL and Nrf2 inhibitors at different concentrations and durations to treat renal tubular epithelial cells; the expression of CD36 and cytoplasmic and nucleic Nrf2 and E-cadherin in those cells were observed by Western blot and reverse-transcription polymerase chain reaction. Results: The protein levels of Nrf2 decreased in expression after 24 hours of OxLDL treatment. At the same time, the Nrf2 protein level in the cytoplasm did not change significantly compared with that of the control group, and the Nrf2 protein level expression in the nucleus increased. Both the messenger ribonucleic acid (mRNA) and protein expression of CD36 decreased following the treatment of cells with the Nrf2 inhibitor Keap1. Kelch-like ECH-associated protein 1 was overexpressed, and CD36 mRNA and protein expression were decreased in OxLDL-treated cells. Following the overexpression of Keap1, E-cadherin expression was reduced in NRK-52E cells. Conclusion: Nuclear factor erythroid 2-related factor 2 can be activated by OxLDL; however, it can only alleviate OxLDL-induced oxidative stress by transferring from the cytoplasm to the nucleus. Additionally, Nrf2 may play a protective role by upregulating CD36.