Cannabinoid Receptor 1/miR-30b-5p Axis Governs Macrophage NLRP3 Expression and Inflammasome Activation in Liver Inflammatory Disease
Cannabinoid Receptor 1/miR-30b-5p Axis Governs Macrophage NLRP3 Expression and Inflammasome Activation in Liver Inflammatory Disease
复制标题
大麻素受体 1/miR-30b-5p 轴控制肝脏炎症性疾病中巨噬细胞 NLRP3 表达和炎症小体激活
DOI：
10.1016/j.omtn.2020.04.010
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发表时间：
2020-04
期刊：
影响因子：
--
通讯作者：
Li Liying
中科院分区：
文献类型：
--
作者：
Yang Le;Tian Lei;Zhang Zhi;Zhou Xuan;Ji Xiaofang;Liu Fuquan;Dong Chengbin;Hou Lei;Zhao Xinhao;Chang Na;Yang Lin;Li Liying
nod样受体（NLR）家族pyrin domain containing 3 （NLRP3）被认为是多种炎症性疾病的重要启动子或启动子。然而，大麻素受体1 （cannabinoid receptor 1, CB1）与巨噬细胞NLRP3炎症小体的关系及其在肝脏炎症中的分子机制尚不清楚。采用四氯化碳（CCl4）或蛋氨酸-胆碱缺乏和高脂肪（MCDHF）饲料诱导小鼠肝损伤模型。从不同的慢性肝病患者获得人肝组织。CCl4-和mcdhf处理小鼠肝组织和巨噬细胞中CB1表达升高，与NLRP3呈正相关。CB1激动剂ACEA（花生四烯基-2′-氯乙胺）促进巨噬细胞NLRP3表达和NLRP3炎性体活化。在CCl4-和mcdhf处理的小鼠中，CB1拮抗剂AM281阻断可降低NLRP3表达、炎性体激活和肝脏炎症。MicroRNA-30b-5p （miR-30b-5p）通过生物信息学数据库与损伤肝脏中下调的mirna交叉筛选，在小鼠和人肝脏中与NLRP3呈负相关。miR-30b-5p通过直接靶向NLRP3参与巨噬细胞中cb1介导的NLRP3炎性体的激活。重要的是，给药miR-30b-5p agomir靶向NLRP3并减轻损伤肝脏的肝脏炎症。总之，CB1/miR-30b-5p轴调节肝脏炎症期间巨噬细胞中NLRP3的表达和NLPR3炎性体的激活，这为肝脏疾病提供了一个潜在的靶点。
Nod-like receptor (NLR) family pyrin domain containing 3 (NLRP3) has been regarded as an important initiator or promoter in multiple inflammatory diseases. However, the relationship between cannabinoid receptor 1 (CB1) and macrophage NLRP3 inflammasome and the corresponding molecular mechanism in liver inflammation remain unclear. Mouse liver injury models were induced by carbon tetrachloride (CCl4) or methionine-choline-deficient and high fat (MCDHF) diet. Human liver tissues were obtained from patients with different chronic liver diseases. CB1 expression was increased in liver tissue and macrophages of CCl4- and MCDHF-treated mice, positively correlated with NLRP3. CB1 agonist ACEA (Arachiodonyl-2'-Chloroethylamide) promoted NLRP3 expression and NLRP3 inflammasome activation in macrophages. CB1 blockade with its antagonist AM281 reduced NLRP3 expression, inflammasome activation, and liver inflammation in CCl4- and MCDHF-treated mice. MicroRNA-30b-5p (miR-30b-5p), screened by the intersection of bioinformatics databases and downregulated miRNAs in injured liver, negatively correlated with NLRP3 in mouse and human liver. miR-30b-5p was involved in CB1-mediated activation of NLRP3 inflammasome in macrophages by directly targeting NLRP3. Importantly, administration of miR-30b-5p agomir targeted NLRP3 and attenuated liver inflammation in the injured liver. Altogether, CB1/miR-30b-5p axis modulates NLRP3 expression and NLPR3 inflammasome activation in macrophages during liver inflammation, which provides a potential target for liver disease.
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影响因子：
25.7
作者：
Li, Changyong;Kong, Yaxian;Li, Liying
通讯作者：
Li, Liying
影响因子：
24.5
作者：
A. Mallat;S. Lotersztajn
通讯作者：
A. Mallat;S. Lotersztajn
DOI：
10.1016/j.omtn.2017.06.005
发表时间：
2017-09-15
期刊：
Molecular therapy. Nucleic acids
影响因子：
--
作者：
Chakraborty C;Sharma AR;Sharma G;Doss CGP;Lee SS
通讯作者：
Lee SS
影响因子：
24.5
作者：
Suk KT;Mederacke I;Gwak GY;Cho SW;Adeyemi A;Friedman R;Schwabe RF
通讯作者：
Schwabe RF
影响因子：
13.5
作者：
Wree, Alexander;Eguchi, Akiko;McGeough, Matthew D.;Pena, Carla A.;Johnson, Casey D.;Canbay, Ali;Hoffman, Hal M.;Feldstein, Ariel E.
通讯作者：
Feldstein, Ariel E.