{"title":"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。","authors":"Mengmeng Pu, Yijun Chen, Dewei Ouyang","doi":"10.1159/000552931","DOIUrl":null,"url":null,"abstract":"<p><strong>Introduction: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":17813,"journal":{"name":"Kidney & blood pressure research","volume":" ","pages":"737-748"},"PeriodicalIF":2.1000,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13493087/pdf/","citationCount":"0","resultStr":"{\"title\":\"LncRNA RAD51-AS1 Alleviates Oxidative Stress and Inflammation in Diabetic Nephropathy by Adsorbing miR-154-5p.\",\"authors\":\"Mengmeng Pu, Yijun Chen, Dewei Ouyang\",\"doi\":\"10.1159/000552931\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Introduction: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>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.</p>\",\"PeriodicalId\":17813,\"journal\":{\"name\":\"Kidney & blood pressure research\",\"volume\":\" \",\"pages\":\"737-748\"},\"PeriodicalIF\":2.1000,\"publicationDate\":\"2026-01-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13493087/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Kidney & blood pressure research\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1159/000552931\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2026/6/24 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q2\",\"JCRName\":\"PERIPHERAL VASCULAR DISEASE\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Kidney & blood pressure research","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1159/000552931","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2026/6/24 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"PERIPHERAL VASCULAR DISEASE","Score":null,"Total":0}
LncRNA RAD51-AS1 Alleviates Oxidative Stress and Inflammation in Diabetic Nephropathy by Adsorbing miR-154-5p.
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.
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.
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
