title: Increased expression of zinc finger protein 267 in non-alcoholic fatty liver disease.
abstract: Hepatocellular lipid accumulation is a hallmark of non-alcoholicfatty liver disease (NAFLD), which encompasses a spectrum ranging from simple steatosis to non-alcoholic steatohepatitis (NASH) and ultimately cirrhosis. Zinc finger protein 267 (ZNF267) belongs to the family of Kruppel-like transcription factors, which regulate diverse biological processes that include development, proliferation, and differentiation. We have previously demonstrated that ZNF267 expression is up-regulated in liver cirrhosis and is further increased in hepatocellular carcinoma (HCC). Here, we analyzed the expression of ZNF267 in tissue specimens of NAFLD patients and found a significant up-regulation compared to normal liver tissue. Noteworthy, ZNF267 mRNA was already significantly increased in steatotic liver tissue without inflammation. In line with this, incubation of primary human hepatocytes with palmitic acid induced a dose-dependent lipid accumulation and corresponding dose-dependent ZNF267 induction in vitro. Furthermore, hepatocellular lipid accumulation induced formation of reactive oxygen species (ROS), and also chemically induced ROS formation increased ZNF267 mRNA expression. In summary with previous findings, which revealed ZNF267 as pro-fibrogenic and pro-cancerogenic factor in chronic liver disease, the present study further suggests ZNF267 as promising therapeutic target particularly for NAFLD patients. In addition, it further indicates that hepatic steatosis per se has pathophysiological relevance and should not be considered as benign.
authors.affiliation: Department of Internal Medicine I, University Hospital Regensburg, Germany.
authors.forename: Bernd
authors.initials: B
authors.lastname: Schnabl
authors.forename: Barbara
authors.initials: B
authors.lastname: Czech
authors.forename: Daniela
authors.initials: D
authors.lastname: Valletta
authors.forename: Thomas S
authors.initials: TS
authors.lastname: Weiss
authors.forename: Georgi
authors.initials: G
authors.lastname: Kirovski
authors.forename: Claus
authors.initials: C
authors.lastname: Hellerbrand
mesh_terms: D002478:Cells, Cultured; D005234:Fatty Liver / Q000235:genetics / Q000378:metabolism*; D022781:Hepatocytes / Q000378:metabolism*; D006801:Humans; D050356:Lipid Metabolism; D008099:Liver / Q000378:metabolism*; D065626:Non-alcoholic Fatty Liver Disease; D019308:Palmitic Acid / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D012097:Repressor Proteins; C502002:ZNF267 protein, human; D019308:Palmitic Acid
references.citation: Phytother Res. 2011 Apr;25(4):588-96
references.pmid: 20925133
references.citation: Exp Mol Pathol. 2011 Dec;91(3):695-701
references.pmid: 21840307
references.citation: Annu Rev Nutr. 1996;16:523-57
references.pmid: 8839937
references.citation: Hepatol Res. 2003 Dec;27(4):289-301
references.pmid: 14662117
references.citation: Biochem Biophys Res Commun. 2001 Sep 7;286(5):1123-30
references.pmid: 11527416
references.citation: Gastroenterology. 2010 Dec;139(6):2146-2157.e12
references.pmid: 20728449
references.citation: Dig Dis Sci. 2010 Mar;55(3):560-78
references.pmid: 20101463
references.citation: Science. 2011 Jun 24;332(6037):1519-23
references.pmid: 21700865
references.citation: Gut. 2008 Feb;57(2):243-51
references.pmid: 17881540
references.citation: Hepatology. 2005 Jul;42(1):44-52
references.pmid: 15895401
references.citation: Diabetes Metab. 2008 Dec;34(6 Pt 2):638-42
references.pmid: 19195624
references.citation: Gastroenterology. 2003 Oct;125(4):1085-93
references.pmid: 14517792
references.citation: Annu Rev Pathol. 2010;5:145-71
references.pmid: 20078219
references.citation: Physiol Rev. 2010 Oct;90(4):1337-81
references.pmid: 20959618
references.citation: Liver Int. 2005 Apr;25(2):357-66
references.pmid: 15780062
references.citation: FASEB J. 2005 Dec;19(14):2085-7
references.pmid: 16234432
references.citation: J Biol Chem. 2009 May 29;284(22):14809-18
references.pmid: 19332540
references.citation: Mol Cell Biol. 2001 Jun;21(11):3609-15
references.pmid: 11340155
references.citation: J Hepatol. 2003 Oct;39(4):538-46
references.pmid: 12971963
references.citation: Hepatology. 2011 Jul;54(1):109-21
references.pmid: 21503941
references.citation: Proc Natl Acad Sci U S A. 1998 Aug 4;95(16):9500-5
references.pmid: 9689109
references.citation: Hepatogastroenterology. 2002 May-Jun;49(45):747-51
references.pmid: 12063983
references.citation: J Exp Clin Cancer Res. 2007 Mar;26(1):117-24
references.pmid: 17550140
references.citation: Diabetes Metab. 2008 Dec;34(6 Pt 2):634-7
references.pmid: 19195623
references.citation: Int J Clin Exp Pathol. 2010 Mar 25;3(5):505-14
references.pmid: 20606731
references.citation: Semin Liver Dis. 2008 Nov;28(4):370-9
references.pmid: 18956293
references.citation: Biochim Biophys Acta. 2000 Dec 1;1494(3):269-76
references.pmid: 11121585
references.citation: Biochem Biophys Res Commun. 2005 Sep 16;335(1):87-96
references.pmid: 16054593
references.citation: Cell Prolif. 2002 Oct;35(5):257-67
references.pmid: 12269903
references.citation: Gastroenterology. 2008 Jul;135(1):282-291.e1
references.pmid: 18515091
references.citation: Gut. 2010 Oct;59(10):1303-7
references.pmid: 20650925
references.citation: Proc Natl Acad Sci U S A. 2004 Mar 30;101(13):4578-83
references.pmid: 15070760
references.citation: Cell Res. 2009 Aug;19(8):996-1005
references.pmid: 19546889
references.citation: Dig Liver Dis. 2010 May;42(5):320-30
references.pmid: 20207596
references.citation: J Biol Chem. 2010 Feb 26;285(9):6044-52
references.pmid: 20032470
references.citation: DNA Cell Biol. 1995 Feb;14(2):125-36
references.pmid: 7865130
references.citation: Free Radic Res. 2007 Jan;41(1):38-49
references.pmid: 17164177