摘要
Objective:This study aimed to explore the expression profile of transcription factor Runt-related transcription factor 2(RUNX2)in the synovial tissues of rheumatoid arthritis(RA)and its effect on the apoptosis of RA fibroblast-like synovial cells(RA-FLS),and to screen new targets for the diagnosis,treatment and prognosis of RA.Methods:The expression and localization of mRNA and protein of RUNX2 in the synovial tissues were detected by real-time quantitative PCR(q PCR)and immunohistochemical staining,respectively.The effect of the expression of exogenous RUNX2 on the apoptosis process of RA-FLS cell line MH7A was investigated by flow cytometry,and the activation of NF-κB signaling pathway was detected by western blotting.Results:The expression of RUNX2 mRNA was significantly higher in the synovial tissues from RA patients,compared to that in the OA patients(P<0.05).RUNX2 protein was mainly localized in the nuclear of the RA synovial cells.Overexpression of exogenous RUNX2 could notably decrease the apoptosis of RA-FLS,which was substantially reversed by pretreatment with SN50,a specific inhibitor of NF-κB pathway.Compared with blank group and negative control group(p CMV6-AC-GFP-vector),the apoptotic rate of exogenous RUNX2 overexpressing(pCMV6-AC-GFP-RUNX2)MH7A cells was significantly decreased(P<0.05).NF-κB signaling pathway activity was significantly increased(P<0.05),and this effect could be effectively reversed by NF-κB signal pathway-specific inhibitor SN5.Conclusion:The high expression of UNX2 in RA synoviocytes could significantly inhibit the spontaneous apoptosis of cells,and it was related to the abnormal activation of NF-κB signaling pathway.In-depth studies of RUNX2/NF-κB signaling pathways will help to identify novel therapeutic targets for RA.
Objective: This study aimed to explore the expres- sion profile of transcription factor Runt-related transcription factor 2 (RUNχ2) in the synovial tissues of rheumatoid arthritis (RA) and its effect on the apoptosis of RA fibroblast-like synovial cells (RA-FLS), and to screen new targets for the diagnosis, treatment and prognosis of RA. Methods: The expression and localization of mRNA and protein of RUNχ2 in the synovial tis- sues were detected by real-time quantitative PCR (qPCR)and immunohistochemical staining, respectively. The effect of the expression of exogenous RUNχ2 on the apoptosis process of RA-FLS cell line MH7A was investigated by flow cytometry, and the activation of NF-κB signaling pathway was detected by western blotting. Results: The expression of RUNχ2 mRNA was significantly higher in the synovial tissues from RA pa- tients, compared to that in the OA patients (P〈0. 05). RUNχ2 protein was mainly localized in the nuclear of the RA synovial cells. Overexpression of exogenous RUNχ2 could notably de- crease the apoptosis of RA-FLS, which was substantially re- versed by pretreatment with SN50, a specific inhibitor of NF-r, J3 pathway. Compared with blank group and negative control group (pCMV6-AC-GFP-vector) , the apoptotic rate of exogenous RUNχ2 overexpressing (pCMV6-AC-GFP-RUNχ2) MH7A cells was significantly decreased(P〈0. 05). NF-κB signaling pathway activity was significantly increased (P〈0. 05) , and this effect could be effectively reversed by NF-κB signal path- way-specific inhibitor SN5. Conclusion: The high expression of UNχ2 in RA synoviocytes could significantly inhibit the spontaneous apoptosis of cells, and it was related to the abnor- mal activation of NF-κB signaling pathway. In-depth studies of RUNχ2/NF-κB signaling pathways will help to identify novel therapeutic targets for RA.
出处
《广西医科大学学报》
CAS
2017年第10期1401-1405,共5页
Journal of Guangxi Medical University
基金
supported by Science and Technology Research Project in Shaanxi province(No.2014K11-03-06-10)
关键词
医疗卫生行业
医学研究
临床治疗
患者
rheumatoid arthritis
apoptosis
RUNχ2
NF-κB
transcriptional regulation