Mechanism of Panax Notoginseng Saponins Regulates HIF-1α/PDHK1 Pathway-mediated Aerobic Oxidation of CD4+ T Cells to Promote Treg Differentiation
10.13748/j.cnki.issn1007-7693.20233188
- VernacularTitle:三七总皂苷调控HIF-1α/PDHK1通路介导的CD4+T细胞有氧氧化促进Treg分化的机制
- Author:
Furong WANG
1
;
Xingyu YAN
1
;
Yu GE
1
;
Yujie BAO
1
;
Lingling ZHOU
1
Author Information
1. Nanjing University of Chinese Medicine, Nanjing 210023, China
- Publication Type:Journal Article
- Keywords:
panax notoginseng saponins ； HIF-1α ； PDHK1； Treg； CD4+T ； FOXP3
- From:
Chinese Journal of Modern Applied Pharmacy
2024;41(8):1015-1020
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE :To observe the regulation of aerobic oxidation mediated by HIF-1α/PDHK1 pathway by PNS, and to explore its mechanism of promoting the differentiation of Naive CD4+T cells into Treg cells.
METHODS
Naive CD4+T cells were isolated from the spleen of C57BL/6 mice by magnetic beads and induced to differentiate into Treg cells for in vitro culture. Naive CD4+T cells were divided into PNS treatment group(5, 10, 20 μg·mL−1), PNS combined with HIF-1α inhibitor(PX-478) group, and the control group was set up. The proportion of Treg cells differentiation was detected by flow cytometry. The expression of HIF-1α and PDHK1 protein was detected by Western blotting. The expression of HIF-1α, PDHK1 and FOXP3 mRNA was detected by real-time fluorescence quantitative PCR. The level of IL-10 in cell culture supernatant was detected by enzyme-linked immunosorbent assay.
RESULTS
PNS could significantly increase the proportion of Treg cells and the secretion level of IL-10, and increase the expression of FOXP3 mRNA in cells. At the same time, the expression of HIF-1α and PDHK1 protein and mRNA was inhibited. When the cells were treated with 10 μmol·L−1 PX-478 and then treated with 10 μg·mL−1 PNS, the expression of PDHK1 and FOXP3 and the differentiation ratio of Treg cells were not significantly different from those treated with 10 μmol·L−1 PX-478 alone.
CONCLUSION
PNS can reduce the expression level of PDHK1 by HIF-1α to enhance the aerobic oxidation of Naive CD4+T cells and promote their differentiation into Treg cells.
