Long non-coding RNA Growth Arrest Specific 5 Regulates the Podocyte Function in Nephrotic Syndrome Development via microRNA-144-5p/Phosphatase And Tensin Homolog.

IF 2.4 4区 医学 Q2 UROLOGY & NEPHROLOGY
Nephrology Pub Date : 2025-04-01 DOI:10.1111/nep.70024
Xinyi Zhang, Huan Tian, Chang Lu, Shen-Ping Xie, Jing-Sheng Ma, Huai-Zhou Chen, Dong-E Tang, Yong Dai, Qiang Yan, Wei Xian
{"title":"Long non-coding RNA Growth Arrest Specific 5 Regulates the Podocyte Function in Nephrotic Syndrome Development via microRNA-144-5p/Phosphatase And Tensin Homolog.","authors":"Xinyi Zhang, Huan Tian, Chang Lu, Shen-Ping Xie, Jing-Sheng Ma, Huai-Zhou Chen, Dong-E Tang, Yong Dai, Qiang Yan, Wei Xian","doi":"10.1111/nep.70024","DOIUrl":null,"url":null,"abstract":"<p><strong>Aim: </strong>This research examined the role and possible regulatory mechanisms of lncRNA GAS5 in the occurrence and progression of primary nephrotic syndrome (PNS) to provide biomarkers for early screening of PNS in the clinic.</p><p><strong>Methods: </strong>RT-qPCR was employed to assess the expression levels of GAS5 and miR-144-5p. ROC analysis was conducted to evaluate their predictive capabilities for PNS. The interaction between GAS5 and miR-144-5p was confirmed using a dual-luciferase assay. Following this, GAS5 overexpression plasmids, along with co-transfected plasmids, were introduced into podocytes to examine their impact on the inflammatory factors, oxidative stress index, cell proliferation and apoptosis. Furthermore, we performed GO and KEGG enrichment analyses, along with PPI analysis, on the target genes of miR-144-5p to speculate on its potential functions and to identify critical genes.</p><p><strong>Results: </strong>The expression levels of GAS5 were decreased while miR-144-5p levels were elevated in PNS patients. The diagnostic approach of serum GAS5 combined with miR-144-5p improved the accuracy of identification. GAS5 was observed to inhibit inflammation and oxidative stress responses and the apoptosis of MPC-5 cells, and enhance cell proliferation. However, the overexpression of miR-144-5p counteracted the effect of GAS5 on podocyte function. Enrichment analysis suggested the miR-144-5p target genes could affect podocyte structure, homeostasis and cell growth. PTEN and STAT3 are identified as critical regulatory targets.</p><p><strong>Conclusion: </strong>The sponging effect of GAS5 on miR-144-5p caused changes in PTEN mRNA expression and could potentially prevent or mitigate PNS. GAS5 is expected to become a potential target for treating PNS.</p>","PeriodicalId":19264,"journal":{"name":"Nephrology","volume":"30 4","pages":"e70024"},"PeriodicalIF":2.4000,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Nephrology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1111/nep.70024","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"UROLOGY & NEPHROLOGY","Score":null,"Total":0}
引用次数: 0

Abstract

Aim: This research examined the role and possible regulatory mechanisms of lncRNA GAS5 in the occurrence and progression of primary nephrotic syndrome (PNS) to provide biomarkers for early screening of PNS in the clinic.

Methods: RT-qPCR was employed to assess the expression levels of GAS5 and miR-144-5p. ROC analysis was conducted to evaluate their predictive capabilities for PNS. The interaction between GAS5 and miR-144-5p was confirmed using a dual-luciferase assay. Following this, GAS5 overexpression plasmids, along with co-transfected plasmids, were introduced into podocytes to examine their impact on the inflammatory factors, oxidative stress index, cell proliferation and apoptosis. Furthermore, we performed GO and KEGG enrichment analyses, along with PPI analysis, on the target genes of miR-144-5p to speculate on its potential functions and to identify critical genes.

Results: The expression levels of GAS5 were decreased while miR-144-5p levels were elevated in PNS patients. The diagnostic approach of serum GAS5 combined with miR-144-5p improved the accuracy of identification. GAS5 was observed to inhibit inflammation and oxidative stress responses and the apoptosis of MPC-5 cells, and enhance cell proliferation. However, the overexpression of miR-144-5p counteracted the effect of GAS5 on podocyte function. Enrichment analysis suggested the miR-144-5p target genes could affect podocyte structure, homeostasis and cell growth. PTEN and STAT3 are identified as critical regulatory targets.

Conclusion: The sponging effect of GAS5 on miR-144-5p caused changes in PTEN mRNA expression and could potentially prevent or mitigate PNS. GAS5 is expected to become a potential target for treating PNS.

长链非编码RNA生长抑制特异性5通过microRNA-144-5p/磷酸酶和紧张素同源物调控肾病综合征发展中的足细胞功能
目的:探讨lncRNA GAS5在原发性肾病综合征(primary nephrotic syndrome, PNS)发生发展中的作用及可能的调控机制,为临床早期筛查PNS提供生物标志物。方法:采用RT-qPCR检测GAS5、miR-144-5p的表达水平。采用ROC分析评估其对PNS的预测能力。GAS5和miR-144-5p之间的相互作用通过双荧光素酶测定得到证实。随后,将GAS5过表达质粒以及共转染质粒引入足细胞,研究其对炎症因子、氧化应激指数、细胞增殖和凋亡的影响。此外,我们对miR-144-5p的靶基因进行了GO和KEGG富集分析,以及PPI分析,以推测其潜在功能并识别关键基因。结果:PNS患者中GAS5表达水平降低,miR-144-5p表达水平升高。血清GAS5联合miR-144-5p的诊断方法提高了鉴定的准确性。GAS5可抑制MPC-5细胞的炎症和氧化应激反应,抑制细胞凋亡,促进细胞增殖。然而,miR-144-5p的过表达抵消了GAS5对足细胞功能的影响。富集分析表明miR-144-5p靶基因可影响足细胞结构、稳态和细胞生长。PTEN和STAT3被认为是关键的调控靶点。结论:GAS5对miR-144-5p的海绵作用导致PTEN mRNA表达改变,可能预防或减轻PNS。GAS5有望成为治疗PNS的潜在靶点。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 求助全文
来源期刊
Nephrology
Nephrology 医学-泌尿学与肾脏学
CiteScore
4.50
自引率
4.00%
发文量
128
审稿时长
4-8 weeks
期刊介绍: Nephrology is published eight times per year by the Asian Pacific Society of Nephrology. It has a special emphasis on the needs of Clinical Nephrologists and those in developing countries. The journal publishes reviews and papers of international interest describing original research concerned with clinical and experimental aspects of nephrology.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信