Dexmedetomidine ameliorates high glucose-induced epithelial-mesenchymal transformation in HK-2 cells through the Cdk5/Drp1/ROS pathway  

作　　者：Fei Wang Weilong Xu Xiaoge Liu Jun Zhang 

机构地区：[1]Department of Anesthesiology,Fudan University Shanghai Cancer Center,Shanghai 200032,China [2]Department of Oncology,Shanghai Medical College,Fudan University,Shanghai 200032,China [3]Department of Anesthesiology,the Affiliated Hospital of Qingdao University,Qingdao 266000,China

出　　处：《Acta Biochimica et Biophysica Sinica》2024年第1期71-81,共11页生物化学与生物物理学报（英文版）

基　　金：This work was supported by the grant from the Medical Guidance Supporting Project from Shanghai Municipal Science and Technology Committee(No.20Y11906200).

摘　　要：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-2cellsvia inhibitionoftheCdk5/Drp1/ROSpathway.

关 键 词：DEXMEDETOMIDINE high glucose epithelial-mesenchymal transformation cyclin-dependent kinase 5 dynamin-related protein 1 

分 类 号：R96[医药卫生—药理学] R692[医药卫生—药学]