Li Baishun, Guo Liyang, He Ying, Tu Xinran, Zhong Jialin, Guan Hongbing, Jiang Yiguo, Jiang Qianzhou
Guangzhou Key Laboratory of Basic and Applied Research of Oral Regenerative Medicine, Department of Operative Dentistry and Endodontics, Affiliated Stomatology Hospital of Guangzhou Medical University, Guangzhou, 510182, Guangdong, China.
School of Public Health of Guangzhou Medical University, Guangzhou, 511436, Guangdong, China.
Mol Biol Rep. 2022 Sep;49(9):8575-8586. doi: 10.1007/s11033-022-07690-w. Epub 2022 Jul 14.
Pulpitis is a commonly seen oral inflammation condition in clinical practice, it can cause much pain for the patient and may induce infections in other systems. Much is still unknown for the pathogenic mechanism of pulpitis. In this work, we discovered that the expression of miR-155 was associated with dental pulpal inflammation both in vivo and in vitro.
Our experiments of LPS stimulated odontoblast cell line MDPC-23 showed miR-155 could act as a positive regulator by increasing the production of pro-inflammatory cytokines IL-1β and IL-6 during inflammatory responses, whereas knockdown of miR-155 can reverse the effects. Bioinformatics analysis demonstrated that SHIP1 is a direct target of miR-155 in odontoblasts, this result was further verified at both mRNA and protein level. Inhibition of miR-155 resulted in the downregulation of inflammation factors, while co-transfection of si-SHIP1 and miR-155 inhibitor promoted the inflammatory responses. Treatment with miR-155 mimic or si-SHIP1 up-regulated the protein level of p-PI3K and p-AKT. By contrast, miR-155 inhibitor exerted the opposite effects. miR-155 mimics could upregulate the gene expression of IL-1β and IL-6. Co-transfection of LY294002 and miR-155 mimic attenuated the inflammatory responses. Consistent with in vitro results, miR-155 mice could alleviate inflammatory response, as well as decrease the activation of p-PI3K and p-AKT, whereas increase the activation of SHIP1.
Our data revealed a novel role for miR-155 in regulation of dental pulpal inflammatory response by targeting SHIP1 through PI3K/AKT signaling pathway.
牙髓炎是临床常见的口腔炎症性疾病，会给患者带来极大痛苦，并可能引发其他系统感染。目前牙髓炎的发病机制仍有许多未知之处。在本研究中，我们发现miR-155的表达在体内和体外均与牙髓炎症相关。
我们对脂多糖刺激的成牙本质细胞系MDPC-23进行实验，结果显示miR-155在炎症反应过程中可通过增加促炎细胞因子IL-1β和IL-6的产生而发挥正向调节作用，而敲低miR-155可逆转这些作用。生物信息学分析表明SHIP1是成牙本质细胞中miR-155的直接靶点，这一结果在mRNA和蛋白质水平均得到进一步验证。抑制miR-155导致炎症因子下调，而共转染si-SHIP1和miR-155抑制剂则促进炎症反应。用miR-155模拟物或si-SHIP1处理可上调p-PI3K和p-AKT的蛋白水平。相比之下，miR-155抑制剂则产生相反的效果。miR-155模拟物可上调IL-1β和IL-6的基因表达。LY294002与miR-155模拟物共转染可减弱炎症反应。与体外实验结果一致，miR-155基因敲除小鼠可减轻炎症反应，同时降低p-PI3K和p-AKT的激活，而增加SHIP1的激活。
我们的数据揭示了miR-155通过PI3K/AKT信号通路靶向SHIP1在调节牙髓炎症反应中的新作用。
