The role of UHRF2 and UBE2V1 in the epithelial-mesenchymal transition of renal tubular epithelial cells induced by high glucose
Diabetic nephropathy(DN)is a major complication of diabetes mellitus and a major causative agent of chronic kidney disease.UBE2V1,as the only E2 enzyme involved in K63 ubiquitination,is involved in the development of diabetic nephropathy,while UHRF2 acts as E3 ubiquitin ligase in the K63 ubiquitination pathway.Real-time fluorescence quantification,gene silencing and overexpression,scratching test,western blot analysis,K63 ubiquitination protein isolation and immunoprecipitation were used to explore the mechanism of UHRF2 and UBE2V1 in the process of epithelial-mesenchymal transition of renal tubular epithelial cells induced by high glucose.It was found that high glucose could increase the expression of UHRF2 and UBE2V1 in renal tubular epithelial cells,leading to the development of epithelial-mesenchymal transition.The expression of epithelial-mesenchymal transition marker proteins a-SMA and ZEB1 was significantly up-regulated in renal tubular epithelial cells cultured with high glucose,while E-cadherin expression was significantly down-regulated.Knocking down of UHRF2 or UBE2V1 inhibited the up-regulation of α-SMA and ZEB1,and weakened the down-regulation of E-cadherin.UBE2V1 may mediate the up-regulation of UHRF2 transcription in renal tubular epithelial cells cultured with high glucose and may increase the ubiquitination of K63 in UHRF2.The results reflect that both UHRF2 and UBE2V1 are involved in the epithelial-mesenchymal transition of renal tubular epithelial cells under the condition of high glucose,which may synergistic promote the fibrosis of diabetic nephropathy.These findings provide a new idea for the treatment of diabetic nephropathy.
万方数据
维普
