Large-scale gene profiling of the liver in a mouse model of chronic, intragastric ethanol infusion

Ion V. Deaciuc; Dennis E. Doherty; Ravshan Burikhanov; Eun Y. Lee; Arnold J. Stromberg; Xuejun Peng; Willem J.S. De Villiers

doi:10.1016/j.jhep.2003.10.021

Large-scale gene profiling of the liver in a mouse model of chronic, intragastric ethanol infusion

Ion V. Deaciuc, Dennis E. Doherty, Ravshan Burikhanov, Eun Y. Lee, Arnold J. Stromberg, Xuejun Peng, Willem J.S. De Villiers

Research output: Contribution to journal › Article › peer-review

48 Scopus citations

Abstract

Background/Aims: The mechanisms underlying alcohol-induced liver injury are not fully elucidated. An approach in this direction would consist of an all-inclusive assessment of gene expression in the liver. The purpose of this study was to perform a comprehensive analysis of gene expression in the livers of mice treated with ethanol by means of intragastric infusion. Methods: An ethanol- or glucose-enriched liquid diet was fed to animals for 4 weeks via a long-term gastrostomy catheter. The animals were killed and plasma alanine:2-oxoglutarate aminotransferase (ALT) assay, liver histology and total RNA analysis by microarray gene technology were performed. Results: Alcohol increased ALT, induced steatosis, necrosis and inflammation. A total of 12,423 genes were analyzed for expression out of which 4867 were expressed by the liver. Alcohol repressed expression of 11 genes, induced expression of 13 genes, and up- or down-regulated expression of 44 and 42 genes >2-fold, respectively. Gene expression analysis identified several genes that have not previously been tested for alcohol effects. Conclusions: This study: (i) expands the knowledge of mechanism(s) of action of ethanol; (ii) indicates novel pathways of ethanol action on the liver, and (iii) illustrates the utility of microarray gene analysis in hepatology research.

Original language	English
Pages (from-to)	219-227
Number of pages	9
Journal	Journal of Hepatology
Volume	40
Issue number	2
DOIs	https://doi.org/10.1016/j.jhep.2003.10.021
State	Published - Feb 2004

Bibliographical note

Funding Information:
This study was supported by NIAAA AA grants nos. 12314 (IVD), 00292 and 12774 (WJSdV), and in part by Research Center for Alcoholic Liver and Pancreatic Diseases—Animal Core of Keck School of Medicine of the University of Southern California, Los Angeles, CA 90089 (P50 AA11999), funded by NIAAA. This material is also the result of work supported with resources and the use of facilities at the Lexington Veterans Administration Center, KY 40536.

Keywords

Alcohol-induced liver injury
Intragastric ethanol infusion
Large-scale gene expression
Necrosis
Steatohepatitis
Total RNA
cDNA microarrays

ASJC Scopus subject areas

Hepatology

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10.1016/j.jhep.2003.10.021

Cite this

@article{58a1db23e0b446e19ec0f2294b884ffa,

title = "Large-scale gene profiling of the liver in a mouse model of chronic, intragastric ethanol infusion",

abstract = "Background/Aims: The mechanisms underlying alcohol-induced liver injury are not fully elucidated. An approach in this direction would consist of an all-inclusive assessment of gene expression in the liver. The purpose of this study was to perform a comprehensive analysis of gene expression in the livers of mice treated with ethanol by means of intragastric infusion. Methods: An ethanol- or glucose-enriched liquid diet was fed to animals for 4 weeks via a long-term gastrostomy catheter. The animals were killed and plasma alanine:2-oxoglutarate aminotransferase (ALT) assay, liver histology and total RNA analysis by microarray gene technology were performed. Results: Alcohol increased ALT, induced steatosis, necrosis and inflammation. A total of 12,423 genes were analyzed for expression out of which 4867 were expressed by the liver. Alcohol repressed expression of 11 genes, induced expression of 13 genes, and up- or down-regulated expression of 44 and 42 genes >2-fold, respectively. Gene expression analysis identified several genes that have not previously been tested for alcohol effects. Conclusions: This study: (i) expands the knowledge of mechanism(s) of action of ethanol; (ii) indicates novel pathways of ethanol action on the liver, and (iii) illustrates the utility of microarray gene analysis in hepatology research.",

keywords = "Alcohol-induced liver injury, Intragastric ethanol infusion, Large-scale gene expression, Necrosis, Steatohepatitis, Total RNA, cDNA microarrays",

author = "Deaciuc, {Ion V.} and Doherty, {Dennis E.} and Ravshan Burikhanov and Lee, {Eun Y.} and Stromberg, {Arnold J.} and Xuejun Peng and {De Villiers}, {Willem J.S.}",

note = "Funding Information: This study was supported by NIAAA AA grants nos. 12314 (IVD), 00292 and 12774 (WJSdV), and in part by Research Center for Alcoholic Liver and Pancreatic Diseases—Animal Core of Keck School of Medicine of the University of Southern California, Los Angeles, CA 90089 (P50 AA11999), funded by NIAAA. This material is also the result of work supported with resources and the use of facilities at the Lexington Veterans Administration Center, KY 40536.",

year = "2004",

month = feb,

doi = "10.1016/j.jhep.2003.10.021",

language = "English",

volume = "40",

pages = "219--227",

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T1 - Large-scale gene profiling of the liver in a mouse model of chronic, intragastric ethanol infusion

AU - Deaciuc, Ion V.

AU - Doherty, Dennis E.

AU - Burikhanov, Ravshan

AU - Lee, Eun Y.

AU - Stromberg, Arnold J.

AU - Peng, Xuejun

AU - De Villiers, Willem J.S.

N1 - Funding Information: This study was supported by NIAAA AA grants nos. 12314 (IVD), 00292 and 12774 (WJSdV), and in part by Research Center for Alcoholic Liver and Pancreatic Diseases—Animal Core of Keck School of Medicine of the University of Southern California, Los Angeles, CA 90089 (P50 AA11999), funded by NIAAA. This material is also the result of work supported with resources and the use of facilities at the Lexington Veterans Administration Center, KY 40536.

PY - 2004/2

Y1 - 2004/2

N2 - Background/Aims: The mechanisms underlying alcohol-induced liver injury are not fully elucidated. An approach in this direction would consist of an all-inclusive assessment of gene expression in the liver. The purpose of this study was to perform a comprehensive analysis of gene expression in the livers of mice treated with ethanol by means of intragastric infusion. Methods: An ethanol- or glucose-enriched liquid diet was fed to animals for 4 weeks via a long-term gastrostomy catheter. The animals were killed and plasma alanine:2-oxoglutarate aminotransferase (ALT) assay, liver histology and total RNA analysis by microarray gene technology were performed. Results: Alcohol increased ALT, induced steatosis, necrosis and inflammation. A total of 12,423 genes were analyzed for expression out of which 4867 were expressed by the liver. Alcohol repressed expression of 11 genes, induced expression of 13 genes, and up- or down-regulated expression of 44 and 42 genes >2-fold, respectively. Gene expression analysis identified several genes that have not previously been tested for alcohol effects. Conclusions: This study: (i) expands the knowledge of mechanism(s) of action of ethanol; (ii) indicates novel pathways of ethanol action on the liver, and (iii) illustrates the utility of microarray gene analysis in hepatology research.

AB - Background/Aims: The mechanisms underlying alcohol-induced liver injury are not fully elucidated. An approach in this direction would consist of an all-inclusive assessment of gene expression in the liver. The purpose of this study was to perform a comprehensive analysis of gene expression in the livers of mice treated with ethanol by means of intragastric infusion. Methods: An ethanol- or glucose-enriched liquid diet was fed to animals for 4 weeks via a long-term gastrostomy catheter. The animals were killed and plasma alanine:2-oxoglutarate aminotransferase (ALT) assay, liver histology and total RNA analysis by microarray gene technology were performed. Results: Alcohol increased ALT, induced steatosis, necrosis and inflammation. A total of 12,423 genes were analyzed for expression out of which 4867 were expressed by the liver. Alcohol repressed expression of 11 genes, induced expression of 13 genes, and up- or down-regulated expression of 44 and 42 genes >2-fold, respectively. Gene expression analysis identified several genes that have not previously been tested for alcohol effects. Conclusions: This study: (i) expands the knowledge of mechanism(s) of action of ethanol; (ii) indicates novel pathways of ethanol action on the liver, and (iii) illustrates the utility of microarray gene analysis in hepatology research.

KW - Alcohol-induced liver injury

KW - Intragastric ethanol infusion

KW - Large-scale gene expression

KW - Necrosis

KW - Steatohepatitis

KW - Total RNA

KW - cDNA microarrays

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SN - 0168-8278

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JO - Journal of Hepatology

JF - Journal of Hepatology

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ER -

Large-scale gene profiling of the liver in a mouse model of chronic, intragastric ethanol infusion

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

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