System Biology Investigation Revealed Lipopolysaccharide and Alcohol-Induced Hepatocellular Carcinoma Resembled Hepatitis B Virus Immunobiology and Pathogenesis

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2023 Jul 14

PMID 37446321

Authors

Vishal S Patil

Darasaguppe R Harish

Ganesh H Sampat

Subarna Roy

Sunil S Jalalpure

Pukar Khanal

Swarup S Gujarathi

Harsha V Hegde

Affiliations

Soon will be listed here.

Abstract

Hepatitis B infection caused by the hepatitis B virus is a life-threatening cause of liver fibrosis, cirrhosis, and hepatocellular carcinoma. Researchers have produced multiple in vivo models for hepatitis B virus (HBV) and, currently, there are no specific laboratory animal models available to study HBV pathogenesis or immune response; nonetheless, their limitations prevent them from being used to study HBV pathogenesis, immune response, or therapeutic methods because HBV can only infect humans and chimpanzees. The current study is the first of its kind to identify a suitable chemically induced liver cirrhosis/HCC model that parallels HBV pathophysiology. Initially, data from the peer-reviewed literature and the GeneCards database were compiled to identify the genes that HBV and seven drugs (acetaminophen, isoniazid, alcohol, D-galactosamine, lipopolysaccharide, thioacetamide, and rifampicin) regulate. Functional enrichment analysis was performed in the STRING server. The network HBV/Chemical, genes, and pathways were constructed by Cytoscape 3.6.1. About 1546 genes were modulated by HBV, of which 25.2% and 17.6% of the genes were common for alcohol and lipopolysaccharide-induced hepatitis. In accordance with the enrichment analysis, HBV activates the signaling pathways for apoptosis, cell cycle, PI3K-Akt, TNF, JAK-STAT, MAPK, chemokines, NF-kappa B, and TGF-beta. In addition, alcohol and lipopolysaccharide significantly activated these pathways more than other chemicals, with higher gene counts and lower FDR scores. In conclusion, alcohol-induced hepatitis could be a suitable model to study chronic HBV infection and lipopolysaccharide-induced hepatitis for an acute inflammatory response to HBV.

Citing Articles

Advances in Understanding Lipopolysaccharide-Mediated Hepatitis: Mechanisms and Pathological Features.

Nakadate K, Saitoh H, Sakaguchi M, Miruno F, Muramatsu N, Ito N Curr Issues Mol Biol. 2025; 47(2).

PMID: 39996800 PMC: 11854089. DOI: 10.3390/cimb47020079.

Gene Expression Aberrations in Alcohol-Associated Hepatocellular Carcinoma.

Petrovic A, Stancl P, Grskovic P, Hancic S, Karlic R, Gasparov S Int J Mol Sci. 2024; 25(19).

PMID: 39408891 PMC: 11476681. DOI: 10.3390/ijms251910558.

References

Heit C, Dong H, Chen Y, Thompson D, Deitrich R, Vasiliou V . The role of CYP2E1 in alcohol metabolism and sensitivity in the central nervous system. Subcell Biochem. 2013; 67:235-47. PMC: 4314297. DOI: 10.1007/978-94-007-5881-0_8. View

Jairam S, Edenberg H . Single-nucleotide polymorphisms interact to affect ADH7 transcription. Alcohol Clin Exp Res. 2014; 38(4):921-9. PMC: 3984380. DOI: 10.1111/acer.12340. View

Brind A, Hurlstone A, Edrisinghe D, Gilmore I, Fisher N, Pirmohamed M . The role of polymorphisms of glutathione S-transferases GSTM1, M3, P1, T1 and A1 in susceptibility to alcoholic liver disease. Alcohol Alcohol. 2004; 39(6):478-83. DOI: 10.1093/alcalc/agh105. View

Zhang M, Wang C, Wang C, Zhao H, Zhao C, Chen Y . Enhanced AMPK phosphorylation contributes to the beneficial effects of Lactobacillus rhamnosus GG supernatant on chronic-alcohol-induced fatty liver disease. J Nutr Biochem. 2015; 26(4):337-44. PMC: 6679353. DOI: 10.1016/j.jnutbio.2014.10.016. View

Raish M, Ahmad A, Alkharfy K, Ahamad S, Mohsin K, Al-Jenoobi F . Hepatoprotective activity of Lepidium sativum seeds against D-galactosamine/lipopolysaccharide induced hepatotoxicity in animal model. BMC Complement Altern Med. 2016; 16(1):501. PMC: 5135812. DOI: 10.1186/s12906-016-1483-4. View

Xie Q, Su Y, Dykema K, Johnson J, Koeman J, De Giorgi V . Overexpression of HGF Promotes HBV-Induced Hepatocellular Carcinoma Progression and Is an Effective Indicator for Met-Targeting Therapy. Genes Cancer. 2013; 4(7-8):247-60. PMC: 3807646. DOI: 10.1177/1947601913501075. View

Huang J, Ren T, Cao S, Zheng S, Hu X, Hu Y . HBx-related long non-coding RNA DBH-AS1 promotes cell proliferation and survival by activating MAPK signaling in hepatocellular carcinoma. Oncotarget. 2015; 6(32):33791-804. PMC: 4741803. DOI: 10.18632/oncotarget.5667. View

Tan A, Koh S, Bertoletti A . Immune Response in Hepatitis B Virus Infection. Cold Spring Harb Perspect Med. 2015; 5(8):a021428. PMC: 4526720. DOI: 10.1101/cshperspect.a021428. View

Tan W, Zhao K, Xiang J, Zhou X, Cao F, Song W . Pyrazinamide alleviates rifampin-induced steatohepatitis in mice by regulating the activities of cholesterol-activated 7α-hydroxylase and lipoprotein lipase. Eur J Pharm Sci. 2020; 151:105402. DOI: 10.1016/j.ejps.2020.105402. View

10.

Tanaka N, Matsubara T, Krausz K, Patterson A, Gonzalez F . Disruption of phospholipid and bile acid homeostasis in mice with nonalcoholic steatohepatitis. Hepatology. 2012; 56(1):118-29. PMC: 6371056. DOI: 10.1002/hep.25630. View

11.

Adamson G, Harman A . A role for the glutathione peroxidase/reductase enzyme system in the protection from paracetamol toxicity in isolated mouse hepatocytes. Biochem Pharmacol. 1989; 38(19):3323-30. DOI: 10.1016/0006-2952(89)90630-8. View

12.

Hill D, DSouza N, Lee E, Burikhanov R, Deaciuc I, de Villiers W . A role for interleukin-10 in alcohol-induced liver sensitization to bacterial lipopolysaccharide. Alcohol Clin Exp Res. 2002; 26(1):74-82. View

13.

Zhang J, Jiao L, Song J, Wu T, Bai H, Liu T . Genetic and Functional Evaluation of the Role of FOXO1 in Antituberculosis Drug-Induced Hepatotoxicity. Evid Based Complement Alternat Med. 2021; 2021:3185874. PMC: 8238576. DOI: 10.1155/2021/3185874. View

14.

You M, Crabb D . Molecular mechanisms of alcoholic fatty liver: role of sterol regulatory element-binding proteins. Alcohol. 2005; 34(1):39-43. DOI: 10.1016/j.alcohol.2004.07.004. View

15.

Czekaj P, Krol M, Limanowka L, Michalik M, Lorek K, Gramignoli R . Assessment of animal experimental models of toxic liver injury in the context of their potential application as preclinical models for cell therapy. Eur J Pharmacol. 2019; 861:172597. DOI: 10.1016/j.ejphar.2019.172597. View

16.

Ohta Y, Matsura T, Kitagawa A, Tokunaga K, Yamada K . Xanthine oxidase-derived reactive oxygen species contribute to the development of D-galactosamine-induced liver injury in rats. Free Radic Res. 2007; 41(2):135-44. DOI: 10.1080/10715760600953842. View

17.

Kruk J, Aboul-Enein H, Kladna A, Bowser J . Oxidative stress in biological systems and its relation with pathophysiological functions: the effect of physical activity on cellular redox homeostasis. Free Radic Res. 2019; 53(5):497-521. DOI: 10.1080/10715762.2019.1612059. View

18.

Bouchard M, Giannakopoulos S, Wang E, Tanese N, Schneider R . Hepatitis B virus HBx protein activation of cyclin A-cyclin-dependent kinase 2 complexes and G1 transit via a Src kinase pathway. J Virol. 2001; 75(9):4247-57. PMC: 114170. DOI: 10.1128/JVI.75.9.4247-4257.2001. View

19.

Qiao L, Wu Q, Lu X, Zhou Y, Fernandez-Alvarez A, Ye L . SREBP-1a activation by HBx and the effect on hepatitis B virus enhancer II/core promoter. Biochem Biophys Res Commun. 2013; 432(4):643-9. DOI: 10.1016/j.bbrc.2013.02.030. View

20.

Zhang T, Ikejima T, Li L, Wu R, Yuan X, Zhao J . Impairment of Mitochondrial Biogenesis and Dynamics Involved in Isoniazid-Induced Apoptosis of HepG2 Cells Was Alleviated by p38 MAPK Pathway. Front Pharmacol. 2017; 8:753. PMC: 5662931. DOI: 10.3389/fphar.2017.00753. View