20 - World Journal of Gastroenterology

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Online Submissions: http://www.wjgnet.com/1007-9327office wjg@wjgnet.com doi:10.3748/wjg.v17.i20.2455 An annual topic highlight: Alcohol and liver, 2011 Natalia A Osna Natalia A Osna, Liver Study Unit, Research Service (151), VA Medical Center, 4101 Woolworth Avenue, Omaha, NE 68105, United States Author contributions: Osna NA wrote this editorial. Correspondence to: Natalia A Osna, MD, PhD, Liver Study Unit, Research Service (151), VA Medical Center, 4101 Woolworth Avenue, Omaha, NE 68105, United States. nosna@unmc.edu Telephone: +1-402-9953576 Fax: +1-402-4490604 Received: January 29, 2011 Revised: March 1, 2011 Accepted: March 8, 2011 Published online: May 28, 2011 Abstract An annual topic highlight: Alcohol and Liver, 2011, covers the important and new aspects of pathogenesis of alcoholic liver diseases (ALD). It includes broad topics ranging from the exacerbation of ALD by infectious (viral) agents (hepatitis C virus and human immunodeficiency virus) to the influence of alcohol on liver fibrogenesis, lipid rafts, autophagy and other aspects. This issue is recommended for both basic scientists and clinicians who are involved in alcoholic liver research. © 2011 Baishideng. All rights reserved. Key words: Liver; Alcohol; Autophagy; Fibrogenesis; Immune cells; Lipid rafts; Mouse models; Hepatitis C; Human immunodeficiency virus Osna NA. An annual topic highlight: Alcohol and liver, 2011. World J Gastroenterol 2011; 17(20): 2455 Available from: URL: http://www.wjgnet.com/1007-9327/full/v17/i20/2455.htm DOI: http://dx.doi.org/10.3748/wjg.v17.i20.2455 This annual topic highlight is the fourth issue of reviews devoted to alcoholic liver diseases (ALD) pathogenesis and treatment. It is one of the most respectful annual series of reviews in alcohol research, and now it has an established audience as well as the contributing authors, who are the leading specialists in alcohol studies, including experts from National Institute on Alcohol Abuse and Alcoholism. Here, we cover new aspects of alcohol research that were not addressed in our previous issues. Because alcohol exposure WJG|www.wjgnet.com 2455 EDITORIAL induces epigenetic changes in liver cells, two articles of this Topic Highlight [1,2] focused on the epigenetic regulation in ALD. Another two articles [3,4] addressed the mechanisms of pro-fibrotic changes in ALD. Several articles [5-7] summarized the available animal models for studying HCV infection based on “second-hit” effects of infections in ALD progression. In addition, other important aspects of ALD pathobiology, such as the role of lipid rafts, microRNAs, MSGT1, hepatic stellate cells and innate immunity and the proteasome inhibitor for ALD treatment are included in this issue [8-12] . This Topic Highlight provides an overview of the most modern literature/approaches in the alcohol research and is strongly recommended for gastroenterologists, hepatologists and scientists who work in this field. REFERENCES World J Gastroenterol 2011 May 28; 17(20): 2455 ISSN 1007-9327 (print) ISSN 2219-2840 (online) © 2011 Baishideng. All rights reserved. 1 Mandrekar P. Epigenetic regulation in alcoholic liver disease. World J Gastroenterol 2011; 17: 2456-2464 2 Moghe A, Joshi-Barve S, Ghare S, Gobejishvili L, Kirpich I, McClain CJ, Barve S. Histone modifications and alcoholinduced liver disease: Are altered nutrients the missing link? World J Gastroenterol 2011; 17: 2465-2472 3 Thompson KJ, McKillop IH, Schrum LW. Targeting collagen expression in alcoholic liver disease. World J Gastroenterol 2011; 17: 2473-2481 4 Aziz-Seible RS, Casey CA. Fibronectin: Functional character and role in alcoholic liver disease. World J Gastroenterol 2011; 17: 2482-2499 5 Szabo G, Zakhari S. Mechanisms of alcohol-mediated hepatotoxicity in human-immunodeficiency-virus-infected patients. World J Gastroenterol 2011; 17: 2500-2506 6 Osna NA, Thomes PG, Donohue TM Jr. Involvement of autophagy in alcoholic liver injury and hepatitis C pathogenesis. World J Gastroenterol 2011; 17: 2507-2514 7 Mercer DF. Animal models for studying hepatitis C and alcohol effects on liver. World J Gastroenterol 2011; 17: 2515-2519 8 Dolganiuc A. Role of lipid rafts in liver health and disease. World J Gastroenterol 2011; 17: 2520-2535 9 Lakner AM, Bonkovsky HL, Schrum LW. microRNAs: Fad or future of liver disease. World J Gastroenterol 2011; 17: 2536-2542 10 Suh YG, Jeong WI. Hepatic stellate cells and innate immunity in alcoholic liver disease. World J Gastroenterol 2011; 17: 2543-2551 11 Schaffert CS. Role of MGST1 in reactive intermediate-induced injury. World J Gastroenterol 2011; 17: 2552-2557 12 Bardag-Gorce F. Proteasome inhibitor treatment in alcoholic liver disease. World J Gastroenterol 2011; 17: 2558-2562 S- Editor Tian L L- Editor Ma JY E- Editor Ma WH May 28, 2011|Volume 17|Issue 20|
Online Submissions: http://www.wjgnet.com/1007-9327office wjg@wjgnet.com doi:10.3748/wjg.v17.i20.2456 Natalia A Osna, MD, PhD, Series Editor Epigenetic regulation in alcoholic liver disease Pranoti Mandrekar Pranoti Mandrekar, Department of Medicine, University of Massachusetts Medical School, 364 Plantation Street, Worcester, MA 01605, United States Author contributions: Mandrekar P solely contributed to this paper. Supported by PHS Grant # AA017545 (to Mandrekar P) and AA017986 (to Mandrekar P) from the National Institute of Alcohol Abuse and Alcoholism, National Institutes of Health Correspondence to: Pranoti Mandrekar, PhD, Department of Medicine, University of Massachusetts Medical School, 364 Plantation Street, Worcester, MA 01605, United States. pranoti.mandrekar@umassmed.edu Telephone: +1-508-8565391 Fax: +1-508-8564770 Received: January 20, 2011 Revised: March 2, 2011 Accepted: March 9, 2011 Published online: May 28, 2011 Abstract Alcoholic liver disease (ALD) is characterized by steatosis or fat deposition in the liver and inflammation, which leads to cirrhosis and hepatocellular carcinoma. Induction of target genes without involving changes in DNA sequence seems to contribute greatly to liver injury. Chromatin modifications including alterations in histones and DNA, as well as post-transcriptional changes collectively referred to as epigenetic effects are altered by alcohol. Recent studies have pointed to a significant role for epigenetic mechanisms at the nucleosomal level influencing gene expression and disease outcome in ALD. Specifically, epigenetic alterations by alcohol include histone modifications such as changes in acetylation and phosphorylation, hypomethylation of DNA, and alterations in miRNAs. These modifications can be induced by alcohol-induced oxidative stress that results in altered recruitment of transcriptional machinery and abnormal gene expression. Delineating these mechanisms in initiation and progression of ALD is becoming a major area of interest. This review summarizes key epigenetic mechanisms that are dysregulated by alcohol in the liver. Alterations by alcohol in histone and DNA modifications, enzymes related to histone acetylation such WJG|www.wjgnet.com 2456 World J Gastroenterol 2011 May 28; 17(20): 2456-2464 ISSN 1007-9327 (print) ISSN 2219-2840 (online) © 2011 Baishideng. All rights reserved. as histone acetyltransferases, histone deacetylases and sirtuins, and methylation enzymes such as DNA methyltransferases are discussed. Chromatin modifications and miRNA alterations that result in immune cell dysfunction contributing to inflammatory cytokine production in ALD is reviewed. Finally, the role of alcohol-mediated oxidative stress in epigenetic regulation in ALD is described. A better understanding of these mechanisms is crucial for designing novel epigenetic based therapies to ameliorate ALD. © 2011 Baishideng. All rights reserved. Key words: Alcohol; Epigenetics; Histones; Acetylation; DNA methylation; miRNA; Genes Peer reviewer: Carlos J Pirola, PhD, FAHA, Medical Research Institute A Lanari, Combatientes de Malvinas 3150, Buenos Aires-1427, Argentina Mandrekar P. Epigenetic regulation in alcoholic liver disease. World J Gastroenterol 2011; 17(20): 2456-2464 Available from: URL: http://www.wjgnet.com/1007-9327/full/v17/i20/2456.htm DOI: http://dx.doi.org/10.3748/wjg.v17.i20.2456 INTRODUCTION TOPIC HIGHLIGHT Chronic alcohol consumption has a significant impact on human health and is identified as a major risk factor for development of liver disease. Alcoholic liver disease (ALD) is one of the leading causes of liver disease mortality worldwide. Alcohol-related liver injury includes a spectrum of pathological conditions in the liver including steatosis, steatohepatitis, cirrhosis and hepatocellular carcinoma. Of the molecular mechanisms studied, epigenetic mechanisms altered by alcohol appear to play a significant role in development and progression of disease. These mechanisms have been identified in parenchymal and non-parenchymal cells in the liver and contribute to induction of fatty liver, inflammation, as well as hepatocyte May 28, 2011|Volume 17|Issue 20|
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Page 3 and 4: Robert JL Fraser, Daw Park Jacob Ge
Page 5 and 6: Italy Donato F Altomare, Bari Piero
Page 7 and 8: Fernando Azpiroz, Barcelona Ramon B
Page 9 and 10: S Contents EDITORIAL TOPIC HIGHLIGH
Page 11: Contents APPENDIX FLYLEAF EDITORS F
Page 17 and 18: Mandrekar P. Epigenetics and alcoho
Page 23 and 24: Moghe A et al . Altered nutrients,
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Page 28 and 29: James SJ. Intracellular S-adenosylh
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perpermeability and endotoxemia pri
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metabolism. Nature 2009; 458: 1131-
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Mercer DF. Hepatitis and alcohol ef
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Dolganiuc A. Role of lipid rafts in
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Lakner AM et al . microRNAs and liv
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Lakner AM et al . microRNAs and liv
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in alcoholic liver steatosis [39,40
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Suh YG et al . HSCs and innate immu
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Suh YG et al . HSCs and innate immu
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Schaffert CS et al . MGST1: Friend
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Bardag-Gorce F. Proteasome inhibito
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Bardag-Gorce F. Proteasome inhibito
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Oh BY et al . siRNA therapy in colo
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A Livin expression (%) 120 100 80 6
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Tumor volume (cm 3 ) Oh BY et al .
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M, Coggi G, Bosari S. Inhibitors of
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Institute, UPMC Montefiore, 7 South
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A B C D E Figure 1 Change in coloni
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Jiang HP et al . Differential prote
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A B C Vespasiani Gentilucci U et al
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Vespasiani Gentilucci U et al . Non
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Instructions to authors ISSN and EI
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Instructions to authors used rather
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Instructions to authors Chaoyang Di
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20 - World Journal of Gastroenterology

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