Downregulation of cathepsin S in dendritic cells inhibits the differentiation of Th17 cells to ameliorate restenosis after vascular injury in diabetes
10.3760/cma.j.cn311282-20231209-00204
- VernacularTitle:树突状细胞组织蛋白酶S的下调抑制Th17细胞的分化以改善糖尿病血管损伤再狭窄
- Author:
Changjiang LI
1
;
Hongyu PENG
;
Songyuan HE
;
Zichao CHENG
;
Jinghua LIU
Author Information
1. 首都医科大学附属北京安贞医院心内科冠心病中心，北京 100029
- Keywords:
Diabetes mellitus;
Cathepsin S;
Dendritic cells;
Perivascular adipose tissue;
Th17 cells
- From:
Chinese Journal of Endocrinology and Metabolism
2024;40(8):681-689
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To explore the role of cathepsin S(CTSS) in diabetic vascular injury-induced restenosis.Methods:(1) Dendritic cells(DCs) were stimulated with different concentrations of glucose, and CTSS was either knocked down or upregulated in dendritic cells using adenovirus transfection. The mRNA and protein expression levels of CTSS were detected by RT-qPCR and Western blot, and the changes of interleukin(IL)-6 levels were assessed using RT-qPCR and ELISA in response to CTSS. (2) The extent of Th17 cell differentiation was evaluated with Flow cytometry when CTSS was downregulated or overexpressed. Levels of ROR-γt, IL-17A, IL-17F, IL-22, and IL-23 were measured. (3) Streptozomycin(STZ, 60 mg/kg) was injected into the intraperitoneal cavity of rats fasted for 12 h to obtain a diabetic rat model, and the restenosis model was obtained by balloon catheter and carotid guidewire injury, and the differentiation degree of Th17 cells in different groups of rats was compared when CTSS was up-regulated and down-regulated.Results:(1) DC viability decreased when stimulated with 35 mmol/L glucose for 48 hours. Compared to the control group, glucose treatment led to a concentration-dependent increase in CTSS and IL-6 levels in DCs( P<0.05). Inhibition of CTSS reduced IL-6 protein levels, while its overexpression increased IL-6 protein levels( P<0.05). (2) Compared with the control group, CTSS inhibition in DC decreased the percentage of Th17 cells in T cells, with decreased protein levels of ROR-γt, IL-17A, IL-17F, IL-22, and IL-23, and vice versa ( P<0.050). (3) After carotid artery injury, CTSS expression was increased in perivascular adipose tissue(PVAT) of rats, and levels of ROR-γt, IL-17A, IL-17F, IL-22, and IL-23 in PVAT were significantly elevated. Down-regulation of CTSS eliminated the glucose-induced enhancement. Conclusion:Inhibition of CTSS in DC reduces Th17 cell differentiation and thereby suppresses restenosis following diabetic vascular injury.
