m6A reader IGF2BP1 accelerates apoptosis of high glucose-induced vascular endothelial cells in a m6A-HMGB1 dependent manner
Anru Liang,
Jianyu Liu,
Yanlin Wei,
Yuan Liao,
Fangxiao Wu,
Jiang Ruan,
Junjun Li
Affiliations
Anru Liang
Department of Burns and Plastic Surgery, The Third Affiliated Hospital of Guangxi Medical University and The Second People’s Hospital of Nanning, Nanning, China
Jianyu Liu
Department of Clinical Laboratory, Guiping People’s Hospital, Guigping, China
Yanlin Wei
Department of Emergency, The People’s Hospital of Guangxi Zhuang Autonomous Region & Guangxi Academy of Medical Sciences, Nanning, China
Yuan Liao
Department of Clinical Laboratory, Guiping People’s Hospital, Guigping, China
Fangxiao Wu
Department of Burns and Plastic Surgery, The Third Affiliated Hospital of Guangxi Medical University and The Second People’s Hospital of Nanning, Nanning, China
Jiang Ruan
Department of Burns and Plastic Surgery, The Third Affiliated Hospital of Guangxi Medical University and The Second People’s Hospital of Nanning, Nanning, China
Junjun Li
Research Center of Medical Sciences, The People’s Hospital of Guangxi Zhuang Autonomous Region & Guangxi Academy of Medical Sciences, Nanning, China
Emerging evidence indicates that N6-methyladenosine (m6A) plays a critical role in vascular biological characteristic. In diabetes mellitus pathophysiology, high glucose (HG)-induced vascular endothelial dysfunction is associated with diabetes vascular complications. Nevertheless, the underlying mechanism of high glucose (HG)-related m6A regulation on vascular endothelial cells is still unclear. Results indicated that m6A reader insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) was up-regulated in HG-treated human umbilical vascular endothelium cells (HUVECs) comparing to normal group. Functionally, results indicated that IGF2BP1 knockdown recovered the proliferation of HUVECs inhibited by HG-administration. Besides, IGF2BP1 knockdown reduced the apoptosis induced by HG-administration. Mechanistically, IGF2BP1 interacted with HMGB1 mRNA and stabilized its expression of m6A-modified RNA. Therefore, these findings provided compelling evidence demonstrating that m6A reader IGF2BP1 contributes to the proliferation and apoptosis of vascular endothelial cells in hyperglycaemia, serving as a target for development of diabetic angiopathy therapeutics.
