Baicalin suppresses type 2 dengue virus-induced autophagy of human umbilical vein endothelial cells by inhibiting the PI3K/AKT pathway
10.12122/j.issn.1673-4254.2024.07.07
- VernacularTitle:黄芩苷通过调控PI3K/AKT信号通路抑制登革病毒感染诱导的人静脉内皮细胞的自噬
- Author:
Yao CHENG
1
;
Yuanying WANG
;
Feiyang YAO
;
Pan HU
;
Mingxian CHEN
;
Ning WU
Author Information
1. 贵州医科大学基础医学院化学与生物化学实验室,贵州 贵阳 561113
- Keywords:
dengue virus;
baicalin;
autophagy;
PI3K/AKT signaling;
human umbilical vein endothelial cells
- From:
Journal of Southern Medical University
2024;44(7):1272-1283
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the effect of type 2 dengue virus(DENV-2)infection on autophagy in human umbilical vein endothelial cells(HUVECs)and the mechanism mediating the inhibitory effect of baicalin against DENV-2 infection.Methods Cultured HUVECs with DENV-2 infection were treated with different concentrations of baicalin,and the changes in autophagy of the cells were detected using transmission electron microscopy.Lyso Tracker Red staining was used to examine pH changes in the lysosomes of the cells,and the expressions of ATG5,beclin-1,LC3,P62,STX17,SNAP29,VAMP8,and PI3K/AKT signaling pathway-related proteins were detected by Western blotting.DENV-2 replication in the cells were evaluated using RT-qPCR.The differentially expressed proteins in DENV-2-infected HUVECs were identified by proteomics screening.Results Treatment with baicalin did not significantly affect the viability of cultured HUVECs.Proteomic studies suggested that the PI3K-AKT pathway played an important role in mediating cell injury induced by DENV-2 infection.The results of RT-qPCR demonstrated that baicalin dose-dependently inhibited DENV-2 replication in HUVECs and produced the strongest inhibitory effect at the concentration of 50 μg/mL.Transmission electron microscopy,Lyso Tracker Red staining,RT-qPCR,and Western blotting all showed significant inhibitory effect of baicalin on DENV-2-induced autophagy in HUVECs.DENV-2 infection of HUVECs caused increased cellular expressions of LC3 and P62 proteins,which were significantly lowered by treatment with LY294002(a PI3K inhibitor).Conclusion Baicalin inhibits DENV-2 replication in HUVECs and suppresses DENV-2-induced cell autophagy by inhibiting the PI3K/AKT signaling pathway.
