2. Academic Validation
  3. 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

  • Front Immunol. 2021 Mar 4:12:603192. doi: 10.3389/fimmu.2021.603192.
Fang Jia 1 2,  Fuxue Deng 3,  Pan Xu 1,  Shiying Li 1,  Xuefu Wang 4,  Peng Hu 1,  Hong Ren 1,  Shiwen Tong 5,  Wenwei Yin 1
Affiliations

Affiliations

  • 1 Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Department of Infectious Diseases, Institute for Viral Hepatitis, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.
  • 2 Department of Endocrinology, The Second Affiliated Hospital of Xi'an Jiaotong University (Xibei Hospital), Xi'an Jiaotong University, Xi'an, China.
  • 3 Department of Cardiovascular Medicine, The Second Affiliated Hospital of Xi'an Jiaotong University (Xibei Hospital), Xi'an Jiaotong University, Xi'an, China.
  • 4 School of Pharmacy, Anhui Medical University, Hefei, China.
  • 5 Department of Clinical Nutrition, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.
PMID: 33746949 DOI: 10.3389/fimmu.2021.603192
Abstract

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.

Keywords

A20; LPS/D-GalN; NOD1; acute liver failure; apoptosis.

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