Assessing Alcohol Genes Targets in Mouse Liver Assessment of Alcohol Genes Targets in Mouse Liver
International Journal of Medical Toxicology and Forensic Medicine,
Vol. 14 No. 4 (2024),
12 October 2024
https://doi.org/10.32598/ijmtfm.v14i4.45497
Abstract
Background: Alcohol is a risk factor for liver diseases. There is a correlation between alcohol consumption and fatty liver disease. Experiences have shown gene expression alteration in the liver following alcohol consumption. Since the molecular mechanism of connection between alcohol consumption and fatty liver disease needs a clear perspective, this study aims to explore the significant genes that are targeted by alcohol in the liver of mice.
Methods: Gene expression profiles of mice livers fed with alcohol were retrieved from the Gene Expression Omnibus (GEO) database and compared with the control samples. Data are pre-evaluated with the GEO2R program, and the significant differentially expressed genes (DEGs) are analyzed via gene expression evaluations and regulatory network assessment.
Results: Among the 25619 dysregulated genes, 78 significant DEGs were pointed out. Gene expression analysis showed that most extremely dysregulated genes are up-regulated and belong to the cytochrome P450 genes family. Finally, cytochrome P450 and glutathione S-transferase genes family, as well as hydroxy-delta-5-steroid dehydrogenase, 3 beta- and steroid delta-isomerase 4, were introduced as the critical targeted genes.
Conclusion: In conclusion, detoxification of xenobiotics, cellular metabolism and homeostasis, the pathogenesis of some liver diseases, synthesis of several prostaglandins and steroid hormones, and inflammation fibrosis in the liver are possibly associated with alcohol consumption.
- Mouse
- Liver
- Gene
- Alcohol
How to Cite
References
Liu SY, Tsai IT, Hsu YC. Alcohol-related liver disease: basic mechanisms and clinical perspectives. International Journal of Molecular Sciences. 2021; 22(10):5170. [DOI:10.3390/ijms22105170] [PMID] [PMCID]
Bataller R, Arteel GE, Moreno C, Shah V. Alcohol-related liver disease: Time for action. Journal of Hepatology. 2019; 70(2):221-2. [DOI:10.1016/j.jhep.2018.12.007] [PMID] [PMCID]
Schwantes-An TH, Darlay R, Mathurin P, Masson S, Liangpunsakul S, Mueller S, et al. Genome-wide association study and meta-analysis on alcohol-associated liver cirrhosis identifies genetic risk factors. Hepatology. 2021; 73(5):1920-31. [DOI:10.1002/hep.31535] [PMID]
Jiang Y, Zhang T, Kusumanchi P, Han S, Yang Z, Liangpunsakul S. Alcohol metabolizing enzymes, microsomal ethanol oxidizing system, cytochrome P450 2E1, catalase, and aldehyde dehydrogenase in alcohol-associated liver disease. Biomedicines. 2020; 8(3):50. [DOI:10.3390/biomedicines8030050] [PMID] [PMCID]
Dong-Chen X, Yong C, Yang X, Chen-Yu S, Li-Hua P. Signaling pathways in Parkinson's disease: Molecular mechanisms and therapeutic interventions.Signal Transduction and Targeted Therapy. 2023; 8(1):73. [DOI:10.1038/s41392-023-01353-3] [PMID] [PMCID]
López B, Ravassa S, Moreno MU, José GS, Beaumont J, González A, et al. Diffuse myocardial fibrosis: Mechanisms, diagnosis and therapeutic approaches. Nature Reviews. Cardiology. 2021; 18(7):479-98. [DOI:10.1038/s41569-020-00504-1] [PMID]
Kanda T, Goto T, Hirotsu Y, Masuzaki R, Moriyama M, Omata M. Molecular mechanisms: Connections between nonalcoholic fatty liver disease, steatohepatitis and hepatocellular carcinoma. International Journal of Molecular Sciences. 2020; 21(4):1525. [DOI:10.3390/ijms21041525] [PMID] [PMCID]
Kisseleva T, Brenner D. Molecular and cellular mechanisms of liver fibrosis and its regression. Gastroenterology & Hepatology. 2021; 18(3):151-66. [DOI:10.1038/s41575-020-00372-7] [PMID]
Malik I, Kelley CP, Wang ET, Todd PK. Author correction: Molecular mechanisms underlying nucleotide repeat expansion disorders. Nature Reviews. Molecular Cell Biology. 2021; 22(9):644. [DOI:10.1038/s41580-021-00396-0] [PMID]
Ramos-Tovar E, Muriel P. Molecular mechanisms that link oxidative stress, inflammation, and fibrosis in the liver. Antioxidants. 2020; 9(12):1279. [DOI:10.3390/antiox9121279] [PMID] [PMCID]
Arjmand B, Khodadoost M, Jahani Sherafat S, Rezaei Tavirani M, Ahmadi N, Rezaei Tavirani S. Introducing critical proteins related to liver ischemia/reperfusion injury. Gastroenterology and Hepatology From Bed to Bench. 2024; 17(1):87-92. [DOI:10.22037/ghfbb.v17i1.2555] [PMID] [PMCID]
Jiang CH, Yuan X, Li JF, Xie YF, Zhang AZ, Wang XL, et al. Bioinformatics-based screening of key genes for transformation of liver cirrhosis to hepatocellular carcinoma. Journal of Translational Medicine. 2020; 18(1):40. [DOI:10.1186/s12967-020-02229-8] [PMID] [PMCID]
Wu C, Zhou Y, Wang M, Dai G, Liu X, Lai L, et al. Bioinformatics analysis explores potential hub genes in nonalcoholic fatty liver disease. Frontiers in Genetics. 2021; 12:772487. [DOI:10.3389/fgene.2021.772487] [PMID] [PMCID]
Sookoian S, Pirola CJ. Systems biology elucidates common pathogenic mechanisms between nonalcoholic and alcoholic-fatty liver disease. Plos One. 2013; 8(3):e58895. [DOI:10.1371/journal.pone.0058895] [PMID] [PMCID]
Feng G, Li XP, Niu CY, Liu ML, Yan QQ, Fan LP, et al. Bioinformatics analysis reveals novel core genes associated with nonalcoholic fatty liver disease and nonalcoholic steatohepatitis. Gene. 2020; 742:144549. [DOI:10.1016/j.gene.2020.144549] [PMID]
Raghu R, Liu CT, Tsai MH, Tang X, Kalari KR, Subramanian S, et al. Transcriptome analysis of garlic-induced hepatoprotection against alcoholic fatty liver [internet]. 2012. [Updated 2018 Jun 14]. Available from: [Link]
Yin HQ, Kim M, Kim JH, Kong G, Kang KS, Kim HL, et al. Differential gene expression and lipid metabolism in fatty liver induced by acute ethanol treatment in mice. Toxicology and Applied Pharmacology. 2007; 223(3):225-33. [DOI:10.1016/j.taap.2007.06.018] [PMID]
Nanji AA, Miao L, Thomas P, Rahemtulla A, Khwaja S, Zhao S, et al. Enhanced cyclooxygenase-2 gene expression in alcoholic liver disease in the rat. Gastroenterology. 1997; 112(3):943-51. [DOI:10.1053/gast.1997.v112.pm9041257] [PMID]
Wang Z, Yao T, Song Z. Involvement and mechanism of DGAT2 upregulation in the pathogenesis of alcoholic fatty liver disease. Journal of Lipid Research. 2010; 51(11):3158-65. [DOI:10.1194/jlr.M007948] [PMID] [PMCID]
McArthur AG, Hegelund T, Cox RL, Stegeman JJ, Liljenberg M, Olsson U, et al. Phylogenetic analysis of the cytochrome P450 3 (CYP3) gene family. Journal of Molecular Evolution. 2003; 57(2):200-11. [DOI:10.1007/s00239-003-2466-x] [PMID]
Strange RC, Spiteri MA, Ramachandran S, Fryer AA. Glutathione-S-transferase family of enzymes. Mutation Research. 2001; 482(1-2):21-6. [DOI:10.1016/S0027-5107(01)00206-8] [PMID]
Manikandan P, Nagini S. Cytochrome P450 structure, function and clinical significance: A review. Current Drug Targets. 2018; 19(1):38-54. [DOI:10.2174/1389450118666170125144557] [PMID]
Villeneuve JP, Pichette V. Cytochrome P450 and liver diseases. Current Drug Metabolism. 2004; 5(3):273-82. [DOI:10.2174/1389200043335531] [PMID]
Fisher CD, Lickteig AJ, Augustine LM, Ranger-Moore J, Jackson JP, Ferguson SS, et al. Hepatic cytochrome P450 enzyme alterations in humans with progressive stages of nonalcoholic fatty liver disease. Drug Metabolism and Disposition. 2009; 37(10):2087-94. [DOI:10.1124/dmd.109.027466] [PMID] [PMCID]
Xu J, Ma HY, Liang S, Sun M, Karin G, Koyama Y, et al. The role of human cytochrome P450 2E1 in liver inflammation and fibrosis. Hepatology Communications. 2017; 1(10):1043-57. [DOI:10.1002/hep4.1115] [PMID] [PMCID]
Board PG, Menon D. Glutathione transferases, regulators of cellular metabolism and physiology. Biochimica et Biophysica Acta. 2013; 1830(5):3267-88. [DOI:10.1016/j.bbagen.2012.11.019] [PMID]
Tew KD, Townsend DM. Glutathione-s-transferases as determinants of cell survival and death. Antioxidants & Redox Signaling. 2012; 17(12):1728-37. [DOI:10.1089/ars.2012.4640] [PMID] [PMCID]
Vairetti M, Di Pasqua LG, Cagna M, Richelmi P, Ferrigno A, Berardo C. Changes in glutathione content in liver diseases: An update. Antioxidants. 2021; 10(3):364. [DOI:10.3390/antiox10030364] [PMID] [PMCID]
- Abstract Viewed: 394 times
- pdf Downloaded: 303 times