NOD1 Agonist Protects Against Lipopolysaccharide and D-Galactosamine-Induced Fatal Hepatitis Through the Upregulation of A20 Expression in Hepatocytes.
NOD1 Agonist Protects Against Lipopolysaccharide and D-Galactosamine-Induced Fatal Hepatitis Through the Upregulation of A20 Expression in Hepatocytes.
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NOD1 激动剂通过上调肝细胞中 A20 的表达来预防脂多糖和 D-半乳糖胺诱导的致命性肝炎。
DOI：
10.3389/fimmu.2021.603192
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发表时间：
2021
影响因子：
7.3
通讯作者：
Yin W
中科院分区：
文献类型：
--
作者：
Jia F;Deng F;Xu P;Li S;Wang X;Hu P;Ren H;Tong S;Yin W
越来越多的证据表明NODs参与肝脏疾病;然而，其潜在机制仍然不清楚。在本研究中，我们分析了NOD 1激动剂预处理对脂多糖（LPS）诱导的D-氨基半乳糖（D-GalN）致敏小鼠急性肝衰竭的影响。我们发现用NOD 1激动剂预处理显著降低LPS/D-GalN诱导的死亡率、血清ALT水平升高和肝细胞凋亡。NOD 1激动剂的保护作用不依赖于肿瘤坏死因子（TNF）-α的抑制。NOD 1激动剂预处理也可减轻TNF-α/D-GalN诱导的凋亡性肝损伤。NOD 1激动剂预处理的小鼠中抗凋亡蛋白A20的表达比对照组更明显，并且A20的敲低消除了NOD 1激动剂对LPS/D-GalN诱导的肝损伤和肝细胞凋亡的保护作用。进一步的实验表明，NOD 1激动剂诱导的A20上调需要枯否细胞和TNF-α的存在。总之，我们的数据强烈表明NOD 1参与了肝损伤的调节，并可能成为肝脏疾病的潜在治疗靶点。
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)-α inhibition. NOD1 agonist pretreatment also attenuated TNF-α/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-α. 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.
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用 NOD1 激动剂局部刺激肝窦内皮细胞可激活 T 细胞并抑制小鼠乙型肝炎病毒复制
影响因子：
4.4
作者：
Huang, Shunmei;Zou, Shi;Wu, Jun
通讯作者：
Wu, Jun
影响因子：
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作者：
Girardin, SE;Travassos, LH;Mengin-Lecreulx, D
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Mengin-Lecreulx, D
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作者：
Kuhla, Angela;Eipel, Christian;Vollmar, Brigitte
通讯作者：
Vollmar, Brigitte
影响因子：
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作者：
Vakili, Sanaz;Ebrahimi, Shadi Sadat Seyyed;Meshkani, Reza
通讯作者：
Meshkani, Reza
影响因子：
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作者：
Seglen, P O
通讯作者：
Seglen, P O