The Roles Of TAZ In The Pathogenesis Of Rheumatoid Arthritis And Its Clinical Significance

[Objective]Previous study has demonstrated that TAZ,a number of the Hippo signaling pathway,can form complex with the key transcription factors RORyt of Th17 cells and can promote the transcription activity of RORyt,thus promoting the differentiation of Th17 cells.This research explores the roles of TAZ in the pathogenesis of RA and its clinical significance,which provides clues to reveal the function of TAZ and its role in diseases,as well as in the laboratory diagnosis and treatment of RA.[Methods]This study includes two parts:(?)Animal model:Collagen-Induced Arthritis(CIA)was induced by chicken type? collagen.The mRNA levels of related genes in Peripheral Blood Mononuclear Cells(PBMCs)or lymph nodes(LN)from mice were used by RT=qPCR.Quantification of Thl and Th17 cells in the LN from mice was detected by Flow cytometry.Comparison of the IL-6 and IL-17A concentration in the sera from mice were inspected by ELISA.(?)Clinical experiments with patient samples:RORyt,TAZ and IL-17 expression in PBMCs from RA patients and healthy control were identified by RT-qPCR.The ROC curves and diagnosis effect evaluation of RORyt,TAZ and IL-17 mRNA were calculated by statistics software.The relationship between TAZ expression and inflammatory indicators(Anti-CCP,RF,CRP,ESR,PCT,IL-6,serum IL-17A and DAS28)were evaluated by correlation analysis.[Results](?)Animal experiments:(1)Among Hippo signaling pathway members,TAZ was highly expressed in CIA mice.(2)In PBMCs and lymph nodes from CIA mice,the expression levels of RORyt,TAZ and IL-17 mRNA was higher than control.(3)TAZ deficiency in T cells alleviated the pathogenic effects of CIA mice.(4)TAZ deficiency in T cells suppressed the differentiation of Th17 cells in CIA mice.(5)TAZ deficiency in T cells reduced the expression of inflammatory cytokines.(?)Clinical experiments with patient samples:(1)The expression levels of RORyt,TAZ and IL-17 mRNA in PBMCs from RA patients was higher than healthy control.(2)There was a linear relationship between TAZ and RORyt,IL-17 mRNA in PBMCs from RA patients.(3)The expression levels of TAZ mRNA in PBMCs from RA patients decreased after treatment.(4)The expression levels of TAZ mRNA in PBMCs from RA patients was closely correlated with clinical laboratory test results(Anti-CCP,ESR,PCT,IL-6,serum IL-17A and DAS28).[Conclusion]Our results from animal experiments and clinical experiments,suggested that TAZ plays a significant role in the pathogenesis of RA.TAZ may participates in the pathogenesis of RA by regulating the differentiation of Th17 cells.Reducing TAZ in T cells can inhibit the development of RA.At the same time,TAZ has important clinical significance in the diagnosis of RA.This study provides new ideas for the treatment and diagnosis of RA.