LncRNA RAD51-AS1 Alleviates Oxidative Stress and Inflammation in Diabetic Nephropathy by Adsorbing miR-154-5p.

IF 2.1 4区医学 Q2 PERIPHERAL VASCULAR DISEASE Kidney & blood pressure research Pub Date : 2026-01-01 Epub Date: 2026-06-24 DOI:10.1159/000552931

Mengmeng Pu, Yijun Chen, Dewei Ouyang

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Abstract

Introduction: Diabetic nephropathy (DN) is one of the severe complications of diabetes. The specific roles and mechanisms of lncRNAs in DN remain to be further elucidated. This study aimed to investigate whether lncRNA RAD51-AS1 participates in oxidative stress and inflammatory responses in DN by regulating the miR-154-5p/MPC2 axis, and to elucidate its potential molecular mechanisms.

Methods: This study included 74 patients with DN, 104 patients with type 2 diabetes alone, and 80 healthy controls, assessing their clinical indexes and gene expression. DN models were established using HK-2 cells treated with high-glucose (HG). Cell proliferation and apoptosis were assessed using CCK-8 assay and flow cytometry. Oxidative stress indicators and inflammatory factors were measured by ELISA. The targeting relationship was validated using dual-luciferase reporter assay.

Results: Clinical studies indicated that serum RAD51-AS1 levels were downregulated in DN patients, and it was positively correlated with estimated glomerular filtration rate while negatively correlated with blood urea nitrogen, serum creatinine, and urinary albumin-to-creatinine ratio. Overexpression of RAD51-AS1 significantly inhibited HG-induced oxidative stress and inflammatory responses in HK-2 cells, manifested as enhanced cell proliferation, suppressed apoptosis, reduced levels of MDA, IL-6, IL-1β, and TNF-α, and increased SOD activity. Furthermore, overexpression of miR-154-5p reversed protective effect of RAD51-AS1 on cell injury. In addition, as an endogenous competitive RNA, RAD51-AS1 adsorbed miR-154-5p, thereby releasing its suppression of the target gene MPC2.

Conclusion: RAD51-AS1 is downregulated in DN, and it regulates MPC2 by adsorbing miR-154-5p, thereby participating in oxidative stress and inflammatory responses in DN. This study elucidated a novel mechanism of RAD51-AS1/miR-154-5p/MPC2 axis in DN pathogenesis, providing potential theoretical basis and new targets for therapy of DN.

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LncRNA RAD51-AS1通过吸附miR-154-5p减轻糖尿病肾病的氧化应激和炎症。

糖尿病肾病（Diabetic nephropathy， DN）是糖尿病的严重并发症之一。lncrna在DN中的具体作用和机制有待进一步阐明。本研究旨在探讨lncRNA RAD51-AS1是否通过调控miR-154-5p/MPC2轴参与DN的氧化应激和炎症反应，并阐明其潜在的分子机制。方法：选取74例DN患者、104例单独2型糖尿病患者和80例健康对照，对其临床指标和基因表达进行评估。以高糖（HG）处理的HK-2细胞建立DN模型。采用CCK-8法和流式细胞术观察细胞增殖和凋亡情况。采用ELISA法检测氧化应激指标和炎症因子。用双荧光素酶报告基因试验验证了靶向关系。通过CCK-8测定、流式细胞术、ELISA和双荧光素酶报告基因测定等实验，检测细胞增殖、凋亡、氧化应激指标、炎症因子和基因间的靶向关系。结果：临床研究表明，DN患者血清RAD51-AS1水平下调，且与eGFR呈正相关，与BUN、Scr、UACR呈负相关。过表达RAD51-AS1可显著抑制hg诱导的HK-2细胞氧化应激和炎症反应，表现为细胞增殖增强，细胞凋亡抑制，MDA、IL-6、IL-1β、TNF-α水平降低，SOD活性升高。此外，miR-154-5p过表达逆转了RAD51-AS1对细胞损伤的保护作用。此外，作为内源性竞争性RNA， RAD51-AS1吸附miR-154-5p，从而释放其对靶基因MPC2的抑制。结论：RAD51-AS1在DN中下调，通过吸附miR-154-5p调控MPC2，从而参与DN的氧化应激和炎症反应。本研究阐明了RAD51-AS1/miR-154-5p/MPC2轴在DN发病中的新机制，为DN的治疗提供了潜在的理论依据和新的靶点。

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来源期刊

Kidney & blood pressure research 医学-泌尿学与肾脏学

CiteScore

4.80

自引率

3.60%

发文量

审稿时长

6-12 weeks

期刊介绍： This journal comprises both clinical and basic studies at the interface of nephrology, hypertension and cardiovascular research. The topics to be covered include the structural organization and biochemistry of the normal and diseased kidney, the molecular biology of transporters, the physiology and pathophysiology of glomerular filtration and tubular transport, endothelial and vascular smooth muscle cell function and blood pressure control, as well as water, electrolyte and mineral metabolism. Also discussed are the (patho)physiology and (patho) biochemistry of renal hormones, the molecular biology, genetics and clinical course of renal disease and hypertension, the renal elimination, action and clinical use of drugs, as well as dialysis and transplantation. Featuring peer-reviewed original papers, editorials translating basic science into patient-oriented research and disease, in depth reviews, and regular special topic sections, ''Kidney & Blood Pressure Research'' is an important source of information for researchers in nephrology and cardiovascular medicine.