miR-410调控STAT3影响Th17细胞分化及系统性红斑狼疮发展机制的研究

Systemic lupus erythematosus is a severe multi-system autoimmune disease with high incidence in Asian and life-threatening complications. By miRNA microarray and qRT-PCR, our previous studies have shown that down regulation of miR-410 is significantly related to the activity states of SLE. The expression levels of miR-410 are significantly associated with its potential target gene STAT3. Base on that STAT3 plays a critical role in Th17 development, and the potent pro-inflammatory activities of Th17 cells can explain a number of pathological features of SLE, we presume that miR-410 may regulate Th17 cell differentiation and influence the development of SLE through down regulation of STAT3.Through qRT-PCR, Western blot and luciferase report assay, this study will confirm the regulation fashion of miR-410 on STAT3. Through Flow cytometry, ELISA and in vivo experiments, we will further explore the impact of miR-410 on Th17 cell differentiation and related cytokines. The connection between miR-410 and the key molecule detected by immunohistochemistry with patients’ activity states will decipher their function on SLE diagnosis and prognosis. Combined in vivo and in vitro experiments with data from clinical samples, this project aims to elucidate the role of miR-410 in SLE development and investigate the possible molecular mechanism in which miR-410 regulate Th17 cell differentiation and SLE disease activity through down regulation of STAT3. This project will benefit improving our knowledge in understanding the pathology of SLE and providing useful clues and possible therapeutic targets for clinical diagnosis and treatment of the disease.

系统性红斑狼疮（SLE）是一种自身免疫系统疾病，发病机制复杂，缺少针对性治疗手段。我们前期通过表达谱芯片分析发现一个新的在SLE患者中表达的miRNA-410，其表达水平与疾病活动性相关，并与其预测靶基因STAT3的表达有显著关联。基于STAT3可以调控Th17细胞生成及IL-17,IL-21的表达，在SLE的病理生理中起关键作用，我们推测：miR-410可能通过对STAT3的调控参与Th17细胞分化进而影响SLE的发展，可能是SLE发病过程中一个潜在诊断靶标及治疗靶点。本研究拟通过细胞水平，动物模型及临床样本三个层面分析，明确miR-410对STAT3的转录调控作用，并探讨miR-410通过调控STAT3影响Th17细胞的转化及SLE发展的分子机制，为SLE的发病机制研究提供新的线索，并为临床SLE的诊治提供新的思路与靶点。

我们前期已经通过表达谱芯片分析发现了在SLE患者中表达的miRNA-410，其表达水平与疾病活动性相关，并与其预测靶基因STAT3的表达有显著关联。基于STAT3可以调控Th17细胞生成及IL-17,IL-21的表达，在SLE的病理生理中起关键作用，我们推测：miR-410可能通过对STAT3的调控参与Th17细胞分化进而影响SLE的发展，可能是SLE发病过程中一个潜在诊断靶标及治疗靶点。本研究通过细胞水平，动物模型及临床样本三个层面分析，明确miR-410对STAT3的转录调控作用，探讨了miR-410通过调控STAT3影响细胞因子的转化及SLE发展的分子机制，在SV40MES13细胞中证实miR-410降低了IL-6的表达，并抑制了纤维化的进展，为SLE的发病机制研究提供新的线索，并为临床SLE的诊治提供的思路与靶点。本项目资助发表了2篇SCI，累计影响因子约7分。