Apigenin regulates Treg/Th17 cells balance reduces the progress of rheumatoid arthritis via miR-181a-5p/SOCS3 signaling pathway
10.12007/j.issn.0258-4646.2024.12.004
- VernacularTitle:芹菜素通过miR-181a-5p/SOCS3信号通路调节Treg/Th17细胞平衡减轻类风湿关节炎进展
- Author:
Ning JIAO
1
;
Ying CHEN
;
Lihua CHANG
Author Information
1. 中国医科大学附属第一医院药学部,沈阳 110002
- Publication Type:Journal Article
- Keywords:
apigenin;
rheumatoid arthritis;
Treg/Th17 cell balance;
miR-181a-5p/SOCS3 signal pathway
- From:
Journal of China Medical University
2024;53(12):1080-1087
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the protective effects of apigenin (API) on the balance of Treg/Th17 cells mediated by the miR-181a-5p/SOCS3 signal pathway in a rat model of rheumatoid arthritis (RA). Methods Wistar rats were randomly divided into control,collagen induced arthritis (CIA),API,API+knockdown control (API+sh-NC),and API+SOCS3 knockdown (API+sh-SOCS3) groups. Inflammatory symptoms of arthritis were evaluated using the arthritis index score and gross observations of paw swelling. Pathological injury to the rat synovium was observed using HE staining. The levels of Th17-related cytokines interleukin (IL)-17A and IL-6 and Treg-related cytokines tumor growth factor (TGF)-β and IL-10 in rat serum were detected using ELISA. The proportions of CD4+IL17A+Th17 cells and CD25+Foxp3+Treg cells in the rat spleen were determined using flow cytometry. The expression of miR-181a-5p and SOCS3 in the synovial tissue of rats was detected using real-time fluorescence quantitative PCR (RT-qPCR) and Western blotting. Dou-ble-luciferase reporter gene experiment was used to verify the combination of miR-181a-5p and SOCS3. Results Compared with the con-trol group,in CIA group,paw swelling and pathological injury of ankle synovium were aggravated,arthritis index score,serum IL-17A and IL-6 levels and CD4+IL-17A+cells in spleen cells were significantly increased,while serum TGF-β and IL-10 levels and CD25+Foxp3+cells in spleen cells were significantly decreased (all P<0.05). Compared with CIA group,paw swelling and pathological injury of ankle synovium in API group and API+sh-NC group were improved,arthritis index score,IL-17A and IL-6 levels in serum and CD4+IL-17A+cells in spleen cells were significantly decreased,while TGF-β and IL-10 levels in serum and CD25+Foxp3+cells in spleen cells were sig-nificantly increased (all P<0.05). Compared with the control group,the expression of miR-181a-5p in the synovial tissue of the CIA group was significantly increased,and the expression of SOCS3 mRNA and protein was significantly decreased (all P<0.05). Compared with the CIA group,the expression of miR-181a-5p in the synovial tissue of the API group was significantly decreased,and the expression of SOCS3 mRNA and protein was significantly increased (all P<0.05). Compared with API group and API+sh-NC group,API+sh-SOCS group paw swelling and pathological injury of ankle synovium were aggravated,arthritis index score,serum IL-17A and IL-6 levels and CD4+IL-17A+cells in spleen cells were significantly increased,while serum TGF-β and IL-10 levels and CD25+Foxp3+cells in spleen cells were signifi-cantly decreased (all P<0.05). Compared with the mimics NC group,the relative luciferase activity of HEK-293T cells transfected with SOCS3-WT in the miR-181a-5p mimics group decreased significantly (P<0.05);however,there was no significant difference in the rel-ative luciferase activity of HEK-293T cells transfected with SOCS3-MUT (P>0.05). Conclusion Apigenin can improve the imbalance of Treg/Th17 cells in RA by downregulating the expression of miR-181a-5p and upregulating the expression of its downstream target gene SOCS3,thus improving joint injury induced by RA.
