Plasmalemmal vesicle-associated proteinalleviates high glucose induced endocytosis dysfunction through Kelch-like epichlorohydrin ECH-associated protein 1/nuclear factor erythroid 2-related factor 2/Maf pathway in human liver sinusoidal endothelial cells
10.3969/j.issn.1006-6187.2025.11.011
- VernacularTitle:质膜膜泡关联蛋白通过Kelch样环氧氯丙烷相关蛋白1/核因子E2相关因子2/Maf蛋白调控高糖诱导人肝窦内皮细胞内吞功能机制的研究
- Author:
Wenhui GUO
1
;
Youzhuo PAN
;
Haoyue LEI
;
Xun LU
;
Qi ZHANG
Author Information
1. 730000 兰州,甘肃中医药大学第一临床医学院
- Publication Type:Journal Article
- Keywords:
Plasmalemmal vesicle-associated protein;
Endocytosis dysfunction;
Caveolin-1;
Human liver sinusoidal endothelial cells
- From:
Chinese Journal of Diabetes
2025;33(11):856-862
- CountryChina
- Language:Chinese
-
Abstract:
Objective To explore the molecular mechanism of plasmalemmal vesicle-associated protein(PLVAP)regulating high glucose(HG)induced endocytosis dysfunction in human liver sinusoidal endothelial cells(HLSECs)through Kelch-like epichlorohydrin ECH-associated protein 1(Keap1)/nuclear factor erythroid 2-related factor 2(Nrf2)/Maf protein.Methods HLSECs were cultured in vitro and divided into normal control(NC)group,high glucose(HG)group,PLVAP overexpression recombinant vector(LV-PLVAP)group,lentivirus empty vector(LV-CON)group,HG+LV-PLVAP+Nrf2 inhibitor(ML385)group,HG+LV-PLVAP+Maf inhibitor(Mafenide)group,HG+LV-CON+ML385 group and HG+LV-CON+Mafenide group.Cell activity was detected by CCK-8 assay.The transfection efficiency of LV-PLVAP was observed by fluorescence microscopy.The fluorescence expression of PLVAP and Nrf2 was detected by immunofluorescence.RT-PCR and western blot were used to detect the mRNA and protein expression of PLVAP,Keap1,Nrf2,and Maf,Caveolin-1(CAV-1).Results A lot of green fluorescence appeared in LV-PLVAP and LV-CON groups,however,no green fluorescence was shown in NC group.Immunofluorescence results showed that PLVAP was expressed in cell membrane;Nrf2 was expressed in cytoplasm,and in HG group,Nrf2 was expressed in nucleus.Compared with NC group,the expression of PLVAP,Keap1 mRNA and protein decreased in HG group(P<0.05 or P<0.01),while the expression of Nrf2,Maf and CAV-1 mRNA and protein increased in HG group(P<0.01).Compared with HG group,the expression of PLVAP,Keap1,Nrf2 mRNA and protein increased in HG+LV-PLVAP group(P<0.01),while the expression of Maf,CAV-1 mRNA and protein decreased in HG+LV-PLVAP group(P<0.01).Compared with HG+LV-PLVAP group,the expression of CAV-1 mRNA and protein increased in HG+LV-PLVAP+ML385 and HG+LV-PLVAP+Mafenide groups(P<0.05 or P<0.01).Conclusions PLVAP regulates the expression of CAV-1 through the Keap1/Nrf2/Maf pathway and then regulates HG induced endocytosis dys-function in HLSECs.Over expression of PLVAP alleviates this pathological reaction.
