Abstract
Epithelial-mesenchymal transformation(EMT)plays an important role in the progression of diabetic nephropathy.Dexmedetomidine(DEX)has shown renoprotective effects against ischemic reperfusion injury;however,whether and how DEX prevents high glucose-induced EMT in renal tubular epithelial cells is incompletely known.Here,we conduct in vitro experiments using HK-2 cells,a human tubular epithelial cell line.Our results demonstrate that high glucose increases the expressions of EMT-related proteins,including Vimentin,Slug,Snail and Twist,while de-creasing the expression of E-cadherin and increasing Cdk5 expression in HK-2 cells.Both Cdk5 knockdown and inhibition by roscovitine increase the expressions of E-cadherin while decreasing the expressions of other EMT-related markers.DEX inhibits Cdk5 expression without affecting cell viability and changes the expressions of EMT-related markers,similar to effects of Cdk5 inhibition.Furthermore,Cdk5 is found to interact with Drp1 at the protein level and mediate the phosphorylation of Drp1.In addition,Drp1 inhibition with mdivi-1 could also restrain the high glucose-induced EMT process in HK-2 cells.Immunofluorescence results show that roscovitine,Mdivi-1 and DEX inhibit high glucose-induced intracellular ROS accumulation,while the oxidant H2O2 eliminates the protective effect of DEX on the EMT process.These results indicate that DEX mitigates high glucose-induced EMT progression in HK-2 cells via inhibition of the Cdk5/Drp1/ROS pathway.
基金项目
Medical Guidance Supporting Project from Shanghai Municipal Science and Technology Committee(20Y11906200)
国家科技期刊平台
NSTL
万方数据