Deficiency of CD147 Attenuated Non-alcoholic Steatohepatitis Progression in an NLRP3-Dependent Manner
Deficiency of CD147 Attenuated Non-alcoholic Steatohepatitis Progression in an NLRP3-Dependent Manner
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CD147 缺乏以 NLRP3 依赖性方式减弱非酒精性脂肪性肝炎进展
DOI：
10.3389/fcell.2020.00784
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发表时间：
2020-08
期刊：
影响因子：
--
通讯作者：
Huijie Bian
中科院分区：
文献类型：
--
作者：
Tian Zhang;Hao Li;Ke Wang;Bing Xu;Zhi-Nan Chen;Huijie Bian
分化簇147(CD147)是一种属于免疫球蛋白超家族的跨膜糖蛋白。CD147的过度表达促进了肝细胞癌的发展，并影响免疫紊乱。尽管CD147在非酒精性脂肪性肝炎(NASH)中的表达增加已有报道，但CD147在NASH中的功能尚未得到评估。首先，我们证实了蛋氨酸胆碱缺乏(MCD)饮食诱导的NASH模型小鼠和NASH患者的肝组织中CD147的表达增加。肝细胞特异性CD147缺失的小鼠表现为NASH表型减弱，包括减少脂肪变性、肝损伤、肝细胞凋亡和炎性细胞因子IL-1β/IL-18的分泌。给予MCD饮食后，NLRP3的表达逐渐增加，CD147的表达也逐渐增加。此外，CD147的缺失抑制了MCD饮食诱导的小鼠和原代肝细胞中的NF-κB/NLRP3信号通路。CypA抑制剂TMN355可减轻肝脏脂肪变性和损伤，抑制NF-κB/NLRP3信号通路。因此，CD147可能通过调节炎症反应在NASH的发病机制中发挥重要作用，CypA/CD147可能成为NASH治疗的靶点。
Cluster of differentiation 147 (CD147) is a transmembrane glycoprotein belonging to the immunoglobulin superfamily. CD147 overexpression has been reported to facilitate the development of hepatocellular carcinoma (HCC) and influence immunologic disorders. Although increased expression of CD147 was reported in non-alcoholic steatohepatitis (NASH), functions of CD147 in NASH have not been evaluated. Firstly, we confirmed that CD147 expression was increased in the liver tissues from methionine-choline-deficient (MCD) diet-induced NASH model mice and NASH patients. Mice with hepatocyte-specific CD147 deletion exhibited attenuated NASH phenotypes, including reduced steatosis, liver injury, hepatocyte apoptosis and inflammatory cytokines IL-1β/IL-18 secretion. Following the administration of the MCD diet, NLRP3 expression was increased gradually along with CD147 expression. Furthermore, CD147 deletion inhibited the NF-κB/NLRP3 signaling pathway in both MCD diet-induced mice and primary hepatocytes. Finally, CypA inhibitor TMN355 attenuated liver steatosis and injury and inhibited NF-κB/NLRP3 signaling pathway. Therefore, our results suggest that CD147 played a vital role in NASH pathogenesis by regulating the inflammatory response, and CypA/CD147 could be attractive therapeutic targets for NASH treatment.
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影响因子：
8.3
作者：
Jin R;Xiao AY;Chen R;Granger DN;Li G
通讯作者：
Li G
影响因子：
29.4
作者：
Miura K;Kodama Y;Inokuchi S;Schnabl B;Aoyama T;Ohnishi H;Olefsky JM;Brenner DA;Seki E
通讯作者：
Seki E
CD147 和/或亲环蛋白 A 在肾脏疾病中的作用
影响因子：
4.6
作者：
Qu X;Wang C;Zhang J;Qie G;Zhou J
通讯作者：
Zhou J
影响因子：
82.9
作者：
Friedman SL;Neuschwander-Tetri BA;Rinella M;Sanyal AJ
通讯作者：
Sanyal AJ
肝脏中的凋亡和坏死性：生死攸关的问题。
DOI：
10.1038/s41575-018-0065-y
发表时间：
2018-12
期刊：
Nature reviews. Gastroenterology & hepatology
影响因子：
--
作者：
Schwabe RF;Luedde T
通讯作者：
Luedde T