The MiR-210-3p Expression Levels In PBMCs From Patients With SLE,RA And Their Correlations With Th17 Cells Related Factors Levels

BackgroundMicro RNAs(mi RNAs) are small, single-stranded, non-coding regulatory RNAs that are involved in regulation of m RNA stability and translation efficiency, and participate in many physiological and pathophysiological processes. Recently, various stresses, including hypoxia, were reported to regulate the expression and function of mi RNAs. Among those, mi R-210 is one of the important hypoxia-induced mi RNAs.Under hypoxic conditions, mi R-210 becomes over-expression in reaction to the stabilization of hypoxia inducing factor-1α(HIF-1α). Moreover, mi R-210 plays crucial roles in negatively regulating Hif1 a expression and Th17 differentiation under hypoxic conditions.Systemic lupus erythematosus(SLE) is much more common in women than men,which is an autoimmune inflammation disease with a broad spectrum of antoantibody production, complement activation, causing immune complex deposition, and resulting in tissue injury with multiple organ involvement. Rheumatoid arthritis(RA)is also chronic systemic inflammatory disease mainly characterized by peripheral symmetrical polysynovitis and variable degrees of bone and cartilage erosion, causing impairment of joint function. Although the etiology and pathogenesis of SLE and RA have not been incompletely understood, recent researches have revealed the significance of Th17 cells in their pathogenesis. Both SLE and RA are Th17cell–mediated chronic autoimmune inflammatory diseases. Furthermore, it has proved that inflammatory environments are relatively hypoxic. Previous studies found HIF-1α was a potential therapeutic target for the treatment of a number of Th17cell–mediated autoimmune diseases. The balance of Th17 cells and regulatory T cells represent an important role in the pathogenesis of inflammation and autoimmune diseases. Evidence shows HIF-1α as a major player in regulating differentiation into the Th17 cells and has a role in modulating the Th17/Treg. Therefore, mi R-210 might be an effective new approach for treating Th17 cells-mediated autoimmune disease,including SLE and RA.ObjectiveThe objective of this study was to evaluate the mi R-210-3p expression levels in peripheral mononuclear blood cells(PBMCs) from patients with SLE, RA and their correlations with clinical features and laboratory measurements. Next, by using the method of ELISA, we analysed the relationship between the expression level of mi R-210-3p and IL-17, IL-21, IL-22 and HIF-1α levels in SLE, RA plasma to investigate the role of mi R-210-3p in the pathogenesis of SLE and RA.MethodsReal-time quantitative reverse transcription polymerase chain reaction(RT-q PCR)was used to detect mi R-210-3p expression levels in PBMCs from 35 patients with SLE, 38 patients with RA and 35 healthy controls. The plasma levels of IL-17, IL-21,IL-22 and HIF-1α were detected by ELISA. Patients with SLE and patients with RA were recruited from the First Affiliated Hospital of Anhui Medical University and Anhui Provincial Hospital. Healthy controls were enrolled from subjects for health check in the First Affiliated Hospital of Anhui Medical University. All patients with SLE met 1997 revised American College of Rheumatology criteria for the classification of SLE. Patients with RA were diagnosed in accordance with the 1987 revised American College of Rheumatology criteria for the classification of RA. Fresh5 ml peripheral blood samples were collected in ethylenediaminetetraacetic acid disodium salt(EDTA-2Na) tubes from each subject. The data of demographic,clinical and laboratory features were also acquired at the same time.All data were analyzed by SPSS 17.0 software(SPSS Inc., USA). Numerical datawere presented as the mean and standard deviation(mean ± SD). Variables not normally distributed were described using the median value and interquartile range(IQR). The differences of mi R-210-3p expression levels were compared using Wilcoxon rank sum test. The correlation between two variables was assessed by Spearman, s correlation coefficients. P<0.05 was considered statistically significant.ResultsCompared with the healthy controls, the mi R-210-3p expression levels were significantly increased in patients with SLE(Z=-3.377, P=0.001) and there was increased significantly expression of mi R-210 in patients with anti-SSB/La antibody-negative group(P=0.038) and pleurisy group(P=0.019). Although no significant difference between mi R-210-3p expression levels in RA patients and those in healthy controls was found(Z=-1.226, P=0.220). There was a positive association between mi R-210-3p levels of active RA patients and inactive patients(Z=-3.116,P=0.002). mi R-210-3p expression levels were significantly associated with plasma IL-17 levels(r=0.357, P=0.028), IL-21 levels(r=0.334, P=0.041)in RA patients. No significant associations were found between plasma HIF-1α levels and mi R-210-3p expression levels in SLE and RA patients.ConclusionsThe dysregulation of mi R-210-3p levels in SLE and RA patients suggest that mi R-210-3p might play a vital role in the pathogenesis of SLE and RA. The mi R-210-3p expression levels were significantly associated with plasma IL-17 levels,IL-21 levels in RA patients show mi R-210-3p plays crucial roles in the pathogenesis of SLE and RA through negatively regulating Th17 differentiation.