Modulation Of IGF1R Signaling Pathway By GIGYF1 In High Glucose-Induced SHSY-5Y Cells

BackgroundDiabetic patients present a high risk of developing cognitive impairment,namely,diabetic encephalopathy(DE),which is clinically manifested as chronic encephalopathy,such as cognitive dysfunction,dementia,and mental disorders.Grb10(growth factor receptor-bound protein 10)-interacting GYF protein 1(GIGYF1)can modulate insulin like growth factor 1 receptor(IGF1R)signaling pathway,which plays an important role in regulating diabetes associated cognitive impairment,by linking to Grb10 adapter.ObjectiveTo investigate the effect of the expression level of GIGYF1 on the IGF1 R signaling pathway and the function of the cells in high glucose induced SHSY-5Y cells.MethodsHuman neuroblastoma cell SHSY-5Y cells were induced by high glucose and GIGYF1-shRNA lentivirus was used to knock down the expression level of GIGYF1.We measured the expression level of GIGYF1,Grb10,phosphorylated IGF1R/IGF1 R,phosphorylated AKT serine/threonine protein kinase/protein kinase B(AKT)/AKT,and phosphorylated extracellular signal-regulated kinase(ERK)/ERK in human neuroblastoma SHSY-5Y cells.Meanwhile,we detected cell apoptosis,proliferation,and migration by Annexin V/PI staining assay,5-Ethynyl-2′-deoxyuridine assay and scratch wound healing assay.ResultsThe percentage of apoptotic cells increased along with the increasing concentrations of glucose(0–200mM).The expression of GIGYF1 had a significant increase in the presence of 25 mM concentration of glucose in SHSY-5Y cells.In addition,high glucose augmented the expression of IGF1 R and Grb10,but decreased the expression of p-IGF1R/IGF1 R,p-AKT/AKT,and p-ERK/ERT.However,GIGYF1 knockdown reversed the decline in the expression of p-IGF1R/IGF1 R,p-AKT/AKT,and p-ERK/ERT to some extent.In addition,knocking down GIGYF1 promoted the proliferation and migration of SHSY-5Y cells,but inhibited the apoptosis in SHSY-5Y cells.ConclusionKnocking down the expression of GIGYF1 can regulate IGF1 R signaling pathway and cell function in high glucose-induced SHSY-5Y cells.