LncRNA在川崎病血管炎中的作用机制研究

Kawasaki disease(KD) is a kind of febrile systemic vasculitis disease in children, and the pathogenesis is still unclear. MAPK/NF-κB signaling pathway and NLRP3 inflammasome were confirmed paly inportant role in coronary injury of Kawasaki disease in previous research. Based on this, we have a further study in gene level. Long noncoding RNAS(lncrnas) play a vital role in various diseases, and become hot research area in life medical. Our previous study found that AC069363.1 was highly expressed in Kawasaki disease children and overexprssion of mrna-CCL3 was found. Furthermore, bioinformatic analysis suggested ACO69363.I promoted MAPK/NF-κB signaling activation by regulating CCL3. This study will firstly verify the relationship between AC069363.1 and KD. Moreover, we will investigate the function of AC069363 I in vitro and in KD aninmal model. Additionally, we will explore the detailed mechanism of Ac 069363.1 interacted with MAPK/NF-κB-NLRP3 pathway. This study have certain creativity and will provide a new potential target for the prevent ion and treatment of KD.

川崎病是一种以全身血管炎性病变为主要特征的急性发热性小儿疾病,其发病机制仍不明确。研究证实MAPK/NF-κB通路及其下游NLRP3炎症小体参与川崎病冠脉损伤的发生,本课题拟在此基础上进一步从基因水平对相关机制进行深入探讨。课题组前期借助高通量测序技术及靶基因功能富集性分析,发现LncRNAAc069363.1及其临近的mRNA-CCL3在川崎病患儿体内显著高表达,并与MAPK/NF-κB通路相关。结合生物信息学分析,提示CCL3-MAPK/NF-κB-NLRP3信号通路为AC069363.1可能参与川崎病血管内皮损伤的机制线索。本研究拟分析AC06936.1在川崎病患儿体内表达规律及与川崎病冠脉损伤的相关性;并从动物模型及细胞水平对AC069363.1完成功能验证,以MAPK/NF-κB-NLRP3为机制主线,论证AC069363.1引起川崎病血管炎性损伤的新机制。

川崎病(Kawasaki disease, KD)又称皮肤粘膜淋巴结综合征，是一种以全身血管炎性病变为主要病理特征的急性发热性出疹性小儿疾病。其主要危害是对心脏及血管的损害，已取代风湿热成为儿科最常见的后天心脏病。川崎病的发病机制目前尚不明确。血管内皮细胞的炎性损伤是冠脉并发症发生发展的基础。本课题旨在从MAPK /NF-κB-NLRP3 信号通路水平，研究lncRNA AC069363.1以及下游的CCL3 mRNA在川崎病血管内皮细胞损伤中的调控作用，为川崎病的发病机制及治疗提供新的思路。研究结果显示川崎病患儿的外周血PBMC细胞中lncRNA AC069363.1、CCL3及NLRP3表达水平较正常儿童组明显升高，且Lnc RNA水平与CCL3、CRP、ESR成正相关，与NLRP3无明显相关；在川崎病细胞模型中lncRNA AC069363.1、CCL3表达水平明显升高，而NLRP3表达水平与对照组相比无明显差异；通过过表达及干扰lncRNA AC069363.1可以正向调控CCL3的表达。在细胞水平过表达lncRNA AC069363.1的可以降低NF-κB p65、p-JNK、ERK蛋白的表达水平。本课题结果提示lncRNA AC069363.1及其下游的CCL3在川崎病中发挥重要作用，且AC069363.1对MAPK及NF-κB通路有调节作用，为川崎病的发病机制研究及治疗方法提供新的思路及靶点。