IGF2BP1-Mediates m

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