NOD1 Agonist Protects Against Lipopolysaccharide and D-Galactosamine-Induced Fatal Hepatitis Through the Upregulation of A20 Expression in Hepatocytes

作者全名："Jia, Fang; Deng, Fuxue; Xu, Pan; Li, Shiying; Wang, Xuefu; Hu, Peng; Ren, Hong; Tong, Shiwen; Yin, Wenwei"

作者地址："[Jia, Fang; Xu, Pan; Li, Shiying; Hu, Peng; Ren, Hong; Yin, Wenwei] Chongqing Med Univ, Key Lab Mol Biol Infect Dis, Dept Infect Dis, Inst Viral Hepatitis,Minist Educ,Affiliated Hosp, Chongqing, Peoples R China; [Jia, Fang] Xi An Jiao Tong Univ, Affiliated Hosp 2, Xibei Hosp, Dept Endocrinol, Xian, Peoples R China; [Deng, Fuxue] Xi An Jiao Tong Univ, Xibei Hosp, Affiliated Hosp 2, Dept Cardiovasc Med, Xian, Peoples R China; [Wang, Xuefu] Anhui Med Univ, Sch Pharm, Hefei, Peoples R China; [Tong, Shiwen] Chongqing Med Univ, Affiliated Hosp 2, Dept Clin Nutr, Chongqing, Peoples R China"

通信作者："Yin, WW (corresponding author), Chongqing Med Univ, Key Lab Mol Biol Infect Dis, Dept Infect Dis, Inst Viral Hepatitis,Minist Educ,Affiliated Hosp, Chongqing, Peoples R China.; Tong, SW (corresponding author), Chongqing Med Univ, Affiliated Hosp 2, Dept Clin Nutr, Chongqing, Peoples R China."

来源：FRONTIERS IN IMMUNOLOGY

ESI学科分类：IMMUNOLOGY

WOS号：WOS:000629983200001

JCR分区：Q1

影响因子：7.3

年份：2021

卷号：12

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：NOD1; A20; acute liver failure; LPS; D-GalN; apoptosis

摘要："Increasing evidence suggests that NODs are involved in liver diseases; however, the underlying mechanisms remain obscure. In the present study, we analyzed the effect of NOD1 agonist pretreatment on acute liver failure induced by lipopolysaccharide (LPS) in D-galactosamine (D-GalN)-sensitized mice. We found that pretreatment with the NOD1 agonist markedly reduced LPS/D-GalN-induced mortality, elevation of serum ALT levels, and hepatocyte apoptosis. The protective effect of NOD1 agonist was independent of tumor necrosis factor (TNF)-alpha inhibition. NOD1 agonist pretreatment also attenuated TNF-alpha/D-GalN-induced apoptotic liver damage. The anti-apoptotic protein A20 expression was more pronounced in NOD1 agonist pretreated mice than in controls, and knockdown of A20 abrogated the protective effect of NOD1 agonist on LPS/D-GalN-induced liver injury and hepatocyte apoptosis. Further experiments showed that NOD1 agonist-induced A20 upregulation required the presence of kupffer cells and TNF-alpha. Taken together, our data strongly indicate that NOD1 is involved in the regulation of liver injury and could be a potential therapeutic target for liver diseases."

基金机构："National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81770570, 81801990]; Program for Outstanding Young Talent of Chongqing Kuanren Hospital and Natural Science Foundation of Chongqing, China [cstc2019jcyj-msxmX0007]; National Science and Technology Major Project of China [2017ZX10202203-007, 2017ZX102 02203-008]"

基金资助正文："This study was funded by the National Natural Science Foundation of China (81770570, 81801990), the Program for Outstanding Young Talent of Chongqing Kuanren Hospital and Natural Science Foundation of Chongqing, China (cstc2019jcyj-msxmX0007), and the National Science and Technology Major Project of China (2017ZX10202203-007, 2017ZX102 02203-008)."