Zhiwen Zhang, Quan Guo, Zhenzhou Zhao, Ming Nie, Qingbo Shi, En Li, Kaiyuan Liu, Haosen Yu, Lixin Rao, Muwei Li
{"title":"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","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":"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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 m<sup>6</sup>A 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.</p><p><strong>Results: </strong>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 m<sup>6</sup>A 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.</p><p><strong>Conclusions: </strong>This study demonstrated that IGF2BP1-mediated m<sup>6</sup>A modification of KLF4 and upregulated ADRM1 affect EndMT in diabetic atherosclerosis.</p>","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":"{\"title\":\"IGF2BP1-Mediates m<sup>6</sup>A 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\":\"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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 m<sup>6</sup>A 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.</p><p><strong>Results: </strong>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 m<sup>6</sup>A 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.</p><p><strong>Conclusions: </strong>This study demonstrated that IGF2BP1-mediated m<sup>6</sup>A modification of KLF4 and upregulated ADRM1 affect EndMT in diabetic atherosclerosis.</p>\",\"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}","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}
IGF2BP1-Mediates m6A Modification of KLF4 and Upregulates ADRM1 to Affect EndMT in Diabetic Atherosclerosis.
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.
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.
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