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Nrf2 在氧化型低密度脂蛋白诱导的肾小管细胞纤维化中的保护作用。

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

机构信息

Nephrology Department, General Hospital of Tianjin Medical University, Tianjin 300052, China.

School of Basic Sciences, Tianjin Medical University, Tianjin 300070, China.

出版信息

Anal Cell Pathol (Amst). 2023 Mar 10;2023:4134928. doi: 10.1155/2023/4134928. eCollection 2023.

Abstract

: 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. : 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. : 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. : 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.

摘要

CD36 是肾小管上皮细胞中氧化型低密度脂蛋白(OxLDL)的受体。核因子红细胞 2 相关因子 2(Nrf2)是激活 Nrf2 信号通路和调节氧化应激的关键因素。Kelch 样 ECH 相关蛋白 1(Keap1)被称为 Nrf2 抑制剂。

我们使用不同浓度和时间的 OxLDL 和 Nrf2 抑制剂处理肾小管上皮细胞;通过 Western blot 和逆转录聚合酶链反应观察细胞中 CD36 和细胞质及核内 Nrf2 和 E-钙黏蛋白的表达。

OxLDL 处理 24 小时后,Nrf2 的蛋白水平降低。同时,与对照组相比,细胞质中 Nrf2 蛋白水平没有明显变化,核内 Nrf2 蛋白水平表达增加。Nrf2 抑制剂 Keap1 处理细胞后,CD36 的信使核糖核酸(mRNA)和蛋白表达均降低。Kelch 样 ECH 相关蛋白 1 过表达,OxLDL 处理的细胞中 CD36 mRNA 和蛋白表达减少。过表达 Keap1 后,NRK-52E 细胞中 E-钙黏蛋白表达减少。

OxLDL 可激活核因子红细胞 2 相关因子 2;然而,它只能通过从细胞质转移到细胞核来缓解 OxLDL 诱导的氧化应激。此外,Nrf2 可能通过上调 CD36 发挥保护作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/16bf/10045629/e2b9a297a73b/ACP2023-4134928.001.jpg

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