N6-methyladenosine (m 6 A) IGF2BP1 regulates high glucose-induced vascular endothelial cells apoptosis via targeting HMGB1

Abstract

In diabetes mellitus pathophysiology, high glucose (HG)-induced vascular endothelial dysfunction is associated with the progress of diabetes vascular complications. Besides, N6-methyladenosine (m6A) has been reported to participate in the vascular biological characteristic. Nevertheless, the underlying mechanisms of high glucose (HG)-related m6A regulation on vascular endothelial cells are still not entirely clear. The proliferation and apoptosis was detected using EdU assay and flow cytometry. The m6A modified level was identified by m6A quantification analysis and MeRIP-PCR. The molecular interaction within IGF2BP1 and HMGB1 was determined by RIP-PCR. Results indicated that m6A reader insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) up-regulated in HG-administrated Human umbilical vascular endothelium cells (HUVECs) as compared to normal glucose group. Functionally, results indicated that IGF2BP1 knockdown recovered the proliferation of HUVECs inhibited by HG-administration. Besides, IGF2BP1 knockdown reduced the apoptosis triggered by HG-administration. Mechanistically, IGF2BP1 interacts with HMGB1 mRNA and stabilized its expression of m6A-modified RNA. Therefore, these findings provide compelling evidence demonstrating that m6A reader IGF2BP1 contributes to the proliferation and apoptosis of vascular endothelial cells in hyperglycaemia, serving as a target for the development of diabetic angiopathy therapeutics.