Bone marrow mesenchymal stem cells inhibit ferroptosis via regulating the Nrf2-keap1/p53 pathway to ameliorate chronic kidney disease injury in the rats.

IF 2.6 4区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Receptors and Signal Transduction Pub Date : 2023-02-01 DOI:10.1080/10799893.2023.2185083

Lishi Shao, Qixiang Fang, Chen Shi, Ya Zhang, Chunjuan Xia, Yifan Zhang, Jiaping Wang, Fukun Chen

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引用次数: 2

Abstract

Purpose: Although bone marrow mesenchymal stem cells (BMMSCs) have been reported to exhibit a protective effect on animal models of chronic kidney disease (CKD), the exact mechanisms involved require further investigation. This study aims to investigate the underlying molecular mechanisms of BMMSCs in inhibiting ferroptosis and preventing an Adriamycin (ADR)-induced CKD injury.

Methods: A rat model of long-term CKD induced through the injection of ADR administered twice weekly via the tail vein was used in this study. After BMMSCs were systemically administered through the renal artery, pathological staining, western blotting, ELISA, and transmission electron microscopy were used to analyze ferroptosis.

Results: Analyses of renal function and histopathological findings indicated that ADR-mediated renal dysfunction improved in response to the BMMSC treatment, which was also sufficient to mediate the partial reversal of renal injury and mitochondrial pathological changes. BMMSCs decreased the ferrous iron (Fe²⁺) and reactive oxygen species and elevated glutathione (GSH) and GSH peroxidase 4. Moreover, the BMMSC treatment activated the expression of ferroptosis-related regulator NF-E2-related factor 2 (Nrf2) and inhibited Keap1 and p53 in CKD rat kidney tissues.

Conclusions: BMMSCs alleviate CKD, possibly resulting from the inhibition of kidney ferroptosis by regulating the Nrf2-Keap1/p53 pathway.

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骨髓间充质干细胞通过调控Nrf2-keap1/p53通路抑制铁凋亡，改善大鼠慢性肾病损伤。

目的:虽然骨髓间充质干细胞(BMMSCs)已被报道对慢性肾脏疾病(CKD)的动物模型显示出保护作用，但其确切机制需要进一步研究。本研究旨在探讨BMMSCs在抑制铁下垂和预防阿霉素(ADR)诱导的CKD损伤中的潜在分子机制。方法:采用每周2次经尾静脉注射ADR致长期CKD大鼠模型。BMMSCs经肾动脉全身给药后，采用病理染色、western blotting、ELISA和透射电镜分析铁下垂。结果:肾功能和组织病理学分析显示，BMMSC治疗后adr介导的肾功能改善，足以介导肾损伤和线粒体病理改变的部分逆转。BMMSCs降低了亚铁(Fe2+)和活性氧，升高了谷胱甘肽(GSH)和谷胱甘肽过氧化物酶4。此外，BMMSC处理激活了铁凋亡相关调节因子nf - e2相关因子2 (Nrf2)的表达，抑制了CKD大鼠肾组织中Keap1和p53的表达。结论:BMMSCs减轻CKD，可能是通过调控Nrf2-Keap1/p53通路抑制肾铁下垂所致。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Receptors and Signal Transduction 生物-生化与分子生物学

CiteScore

6.60

自引率

0.00%

发文量

审稿时长

>12 weeks

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