缺氧微环境下miR-22/HIF-1α/NLRP3信号通路参与牙髓炎发生发展的功能和机制研究

Pulpitis has a double side effect. Moderate inflammatory responses not only effectively defense against invading pathogens, but also promote the pulp tissue repair. However, excessive inflammation leads to pulp tissue necrosis. Therefore, how to control pulpitis is the key factor to protecting the pulp tissue and promoting the tooth repair. The tooth represents a specialized environment with low compliance with a limited tissue swelling capacity and relatively poor lymphatic drainage system. Inevitable, the dental pulp is trapped in hypoxia conditions when encountering inflammation. Our previous study has demonstrated the increase of HIF-1α expression in according with the activation of NLRP3/CASP1 inflammasome pathway, but the decrease of miR-22 expression during the reversible pulpitis development into the irreversible pulpitis. Additionally, we found that both of HIF-1α and NLRP3 3’UTR have the potential binding sites for miR-22, which indicate miR-22 involved in the transcription regulation of HIF-1α and NLRP3.On this basis, this program aims to investigate the regulatory effect of miR-22/HIF-1α/NLRP3 signaling on NLRP3/CASP1 inflammasome pathway mediated pulpitis by clinical research, in vitro cell culture, as well as molecular biology technology. This study represents a significant advance in better revealing the pathogenesis of pulpitis and the mechanism of pulp tissue repair after inflammation and damage, as well as providing a promising therapeutic strategy for future endodontic treatment.

牙髓炎症反应是一把“双刃剑”，适度的炎症反应能有效清除有害物质，还能促进其自我修复，而过度的炎症反应将导致牙髓坏死。因此如何控制牙髓炎是保护牙髓组织，促进牙体损伤再修复的关键。牙髓腔由于特殊的解剖结构，一旦发生炎症，将处于缺氧的环境。课题组前期发现牙髓炎从可逆性向不可逆性进展的过程中缺氧诱导因子1α(HIF-1α)表达升高，NLRP3/CASP1炎症体通路活化，而miR-22表达降低；同时还发现miR-22与 NLRP3和HIF-1α 3’UTR区存在结合位点，参与了转录后调控。据此，本课题拟通过临床样本研究、体外细胞培养、分子生物学技术等方法，分析在龋病、牙髓炎进展的过程中，miR-22/HIF-1α/NLRP3信号通路对NLRP3/CASP1炎症体通路介导的牙髓炎症反应的调控机制，为揭示牙髓炎的发病机理，进而探索牙髓在炎症、损伤后的修复转归机制，为牙髓炎的治疗方法提供新靶点和思路。