IGF2BP1-Mediates m⁶A Modification of KLF4 and Upregulates ADRM1 to Affect EndMT in Diabetic Atherosclerosis.

IF 1.8 4区医学 Q3 CARDIAC & CARDIOVASCULAR SYSTEMS

Acta Cardiologica Sinica Pub Date : 2025-09-01 DOI:10.6515/ACS.202509_41(5).20250104A

Zhiwen Zhang, Quan Guo, Zhenzhou Zhao, Ming Nie, Qingbo Shi, En Li, Kaiyuan Liu, Haosen Yu, Lixin Rao, Muwei Li

{"title":"IGF2BP1-Mediates m6A Modification of KLF4 and Upregulates ADRM1 to Affect EndMT in Diabetic Atherosclerosis.","authors":"Zhiwen Zhang, Quan Guo, Zhenzhou Zhao, Ming Nie, Qingbo Shi, En Li, Kaiyuan Liu, Haosen Yu, Lixin Rao, Muwei Li","doi":"10.6515/ACS.202509_41(5).20250104A","DOIUrl":null,"url":null,"abstract":"Background: Atherosclerosis accelerates the progression of diabetes and metabolic syndrome. Endothelial to mesenchymal transition (EndMT) has been reported to promote the development of atherosclerosis and the generation of extracellular matrix. However, the mechanism of EndMT in diabetic atherosclerosis has not been fully clarified.Methods: Human umbilical vein endothelial cells (HUVECs) were treated with high glucose (HG) and transforming growth factor beta 1 (TGF-β1) to induce EndMT. The levels of insulin-like growth factor 2 mRNA-binding protein (IGF2BP), Krüppel-like factor 4 (KLF4), Adhesion-regulating molecule 1 (ADRM1), CD31, vWF, α-SMA and vimentin were detected by qRT-PCR and Western blot. Correlations among IGF2BP1, KLF4 and ADRM1 were analyzed by RIP and ChIP assays. MeRIP-qPCR was used to detect the m6A level. The effect of IGF2BP1 on the stability of KLF4 was detected by RNA stability assay. Wound healing and Transwell assays were used to detect HUVEC migration ability.Results: IGF2BP1, KLF4 and ADRM1 were upregulated in the diabetic atherosclerosis cell model, and IGF2BP1 knockdown inhibited HG combined with TGF-β1-induced EndMT in HUVECs. Mechanically, IGF2BP1 regulated the m6A level of KLF4. Functionally, IGF2BP1 upregulated KLF4 to promote HG combined with TGF-β1-induced EndMT in HUVECs. The results proved that IGF2BP1 regulated the KLF4/ADRM1 axis promoting EndMT in diabetic atherosclerosis.Conclusions: This study demonstrated that IGF2BP1-mediated m6A modification of KLF4 and upregulated ADRM1 affect EndMT in diabetic atherosclerosis.","PeriodicalId":6957,"journal":{"name":"Acta Cardiologica Sinica","volume":"41 5","pages":"598-611"},"PeriodicalIF":1.8000,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12463961/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Acta Cardiologica Sinica","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.6515/ACS.202509_41(5).20250104A","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"CARDIAC & CARDIOVASCULAR SYSTEMS","Score":null,"Total":0}

引用次数: 0

Abstract

Background: Atherosclerosis accelerates the progression of diabetes and metabolic syndrome. Endothelial to mesenchymal transition (EndMT) has been reported to promote the development of atherosclerosis and the generation of extracellular matrix. However, the mechanism of EndMT in diabetic atherosclerosis has not been fully clarified.

Methods: Human umbilical vein endothelial cells (HUVECs) were treated with high glucose (HG) and transforming growth factor beta 1 (TGF-β1) to induce EndMT. The levels of insulin-like growth factor 2 mRNA-binding protein (IGF2BP), Krüppel-like factor 4 (KLF4), Adhesion-regulating molecule 1 (ADRM1), CD31, vWF, α-SMA and vimentin were detected by qRT-PCR and Western blot. Correlations among IGF2BP1, KLF4 and ADRM1 were analyzed by RIP and ChIP assays. MeRIP-qPCR was used to detect the m⁶A level. The effect of IGF2BP1 on the stability of KLF4 was detected by RNA stability assay. Wound healing and Transwell assays were used to detect HUVEC migration ability.

Results: IGF2BP1, KLF4 and ADRM1 were upregulated in the diabetic atherosclerosis cell model, and IGF2BP1 knockdown inhibited HG combined with TGF-β1-induced EndMT in HUVECs. Mechanically, IGF2BP1 regulated the m⁶A level of KLF4. Functionally, IGF2BP1 upregulated KLF4 to promote HG combined with TGF-β1-induced EndMT in HUVECs. The results proved that IGF2BP1 regulated the KLF4/ADRM1 axis promoting EndMT in diabetic atherosclerosis.

Conclusions: This study demonstrated that IGF2BP1-mediated m⁶A modification of KLF4 and upregulated ADRM1 affect EndMT in diabetic atherosclerosis.

查看原文本刊更多论文

igf2bp1介导KLF4的m6A修饰并上调ADRM1影响糖尿病动脉粥样硬化的EndMT

背景：动脉粥样硬化加速糖尿病和代谢综合征的进展。内皮到间充质转化（EndMT）促进动脉粥样硬化的发展和细胞外基质的生成。然而，EndMT在糖尿病动脉粥样硬化中的作用机制尚未完全阐明。方法：采用高糖（HG）和转化生长因子β1 （TGF-β1）处理人脐静脉内皮细胞（HUVECs）诱导EndMT。采用qRT-PCR和Western blot检测各组大鼠胰岛素样生长因子2 mrna结合蛋白（IGF2BP）、kr pbel样因子4 （KLF4）、黏附调节分子1 （ADRM1）、CD31、vWF、α-SMA和vimentin水平。通过RIP和ChIP分析IGF2BP1、KLF4和ADRM1之间的相关性。采用MeRIP-qPCR检测m6A水平。通过RNA稳定性实验检测IGF2BP1对KLF4稳定性的影响。伤口愈合和Transwell试验检测HUVEC迁移能力。结果：IGF2BP1、KLF4和ADRM1在糖尿病动脉粥样硬化细胞模型中表达上调，IGF2BP1敲低可抑制HG联合TGF-β1诱导的HUVECs EndMT。IGF2BP1在机械上调控KLF4的m6A水平。在功能上，IGF2BP1上调KLF4，促进HG与TGF-β1诱导的HUVECs EndMT结合。结果证明IGF2BP1在糖尿病动脉粥样硬化中调控KLF4/ADRM1轴促进EndMT。结论：本研究表明igf2bp1介导的KLF4的m6A修饰和ADRM1的上调影响糖尿病动脉粥样硬化的EndMT。

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

Acta Cardiologica Sinica 医学-心血管系统

CiteScore

2.90

自引率

15.80%

发文量

144

审稿时长

>12 weeks

期刊介绍： Acta Cardiologica Sinica welcomes all the papers in the fields related to cardiovascular medicine including basic research, vascular biology, clinical pharmacology, clinical trial, critical care medicine, coronary artery disease, interventional cardiology, arrythmia and electrophysiology, atherosclerosis, hypertension, cardiomyopathy and heart failure, valvular and structure cardiac disease, pediatric cardiology, cardiovascular surgery, and so on. We received papers from more than 20 countries and areas of the world. Currently, 40% of the papers were submitted to Acta Cardiologica Sinica from Taiwan, 20% from China, and 20% from the other countries and areas in the world. The acceptance rate for publication was around 50% in general.