title: Flotillin-2 expression in the human gut: from a cell model to human tissue in health and inflammatory bowel diseases.
abstract: OBJECTIVE
  The etiopathogenesis of inflammatory bowel diseases (IBD) remains largely unexplained. Flotillins (flotillin-1 and flotillin-2) are ubiquitous proteins which have been linked to inflammation and regeneration. We hypothesized that alterations in the expression of flotillin-2 in enterocytes may be related to the pathogenesis of IBD as a classical example of an inflammatory disorder of mostly unknown origin.
  
  
  METHODS
  Cell and tissue localization of flotillin-2 (and -1) were investigated by immunofluorescent staining in 1. polarized and unpolarized CaCo-2w cells as a model of human enterocytes (native and after TNFα stimulation) and 2. intestinal biopsies from controls, patients with ulcerative colitis (UC) and patients with Crohn's disease (CD). For quantification of flotillin-2, we analyzed its expression in ileal and colonic biopsies from controls, UC patients and CD patients using real-time RT-PCR, Western blot and indirect immunofluorescence.
  
  
  RESULTS
  In polarized CaCo-2w cells and human enterocytes in biopsies, flotillins were localized at the basolateral membrane and on subapical vesicles, but not in the apical membrane. Flotillin-2 expression did not differ between UC patients, CD patients and controls. However, it was significantly higher in colonic biopsies compared to ileal biopsies in all groups.
  
  
  CONCLUSIONS
  By virtue of its abundant expression in enterocytes, flotillin-2 must have an essential function in intestinal physiology, especially in the colon. Yet our data could not link flotillin-2 to the pathogenesis of IBD.
authors: University Hospital Heidelberg, Department of Gastroenterology, Im Neuenheimer Feld 410, 69120 Heidelberg, Germany.
authors: Annika
authors: A
authors: Gauss
authors: Inga
authors: I
authors: Buchholz
authors: Alexandra
authors: A
authors: Zahn
authors: Gerd
authors: G
authors: Schmitz
authors: Wolfgang
authors: W
authors: Stremmel
authors: Joachim
authors: J
authors: Fuellekrug
authors: Robert
authors: R
authors: Ehehalt
mesh_terms: D000328:Adult; D018938:Caco-2 Cells; D003093:Colitis, Ulcerative / Q000378:metabolism; D003424:Crohn Disease / Q000378:metabolism; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D015212:Inflammatory Bowel Diseases / Q000378:metabolism; D008297:Male; D021962:Membrane Microdomains / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism*; D008875:Middle Aged
chemical_list: D008565:Membrane Proteins; C106354:flotillins
keywords: Crohn's disease; Flotillin-1; Flotillin-2.; Inflammatory bowel disease (IBD); Lipid raft; Ulcerative colitis
references: J Cell Sci. 2004 Aug 1;117(Pt 17):4007-14
references: 15286178
references: Proc Natl Acad Sci U S A. 2003 Jul 8;100(14):8241-6
references: 12826615
references: Gastroenterology. 2012 Oct;143(4):995-1005.e12
references: 22732732
references: Immunity. 2003 May;18(5):655-64
references: 12753742
references: Curr Opin Lipidol. 2002 Oct;13(5):513-21
references: 12352015
references: J Neurobiol. 1998 Dec;37(4):502-23
references: 9858255
references: Cell Mol Life Sci. 2005 Oct;62(19-20):2228-40
references: 16091845
references: Eur J Cell Biol. 2008 Apr;87(4):211-26
references: 18237819
references: Gut. 2005 Jul;54(7):966-71
references: 15951544
references: J Biol Chem. 1999 Apr 30;274(18):12702-9
references: 10212252
references: Ann Intern Med. 2007 Nov 6;147(9):603-10
references: 17975182
references: Methods Enzymol. 1990;182:50-68
references: 2314256
references: J Clin Invest. 2007 Mar;117(3):514-21
references: 17332878
references: Mol Biol Cell. 2000 Aug;11(8):2775-91
references: 10930469
references: Cell Microbiol. 2005 May;7(5):613-20
references: 15839890
references: J Biol Chem. 2001 May 25;276(21):18507-12
references: 11279173
references: Traffic. 2005 Sep;6(9):725-40
references: 16101677
references: Mol Membr Biol. 2006 Jan-Feb;23(1):71-9
references: 16611582
references: Biochem J. 2007 Apr 15;403(2):313-22
references: 17206938
references: FASEB J. 2004 Nov;18(14):1731-3
references: 15345693
references: World J Gastroenterol. 2007 Mar 21;13(11):1687-95
references: 17461471
references: Development. 1997 Jan;124(2):577-87
references: 9053333
references: Am J Pathol. 2004 Nov;165(5):1465-77
references: 15509518
references: Gut Pathog. 2009 Feb 03;1(1):2
references: 19338680
references: J Biol Chem. 2007 Sep 14;282(37):27155-27164
references: 17636253
references: Virol J. 2011 Oct 25;8:479
references: 22023811
references: Gut. 1996 Nov;39(5):684-9
references: 9026483
references: Clin Immunol. 2003 Aug;108(2):138-51
references: 12921760
references: Am J Physiol Gastrointest Liver Physiol. 2012 Apr 15;302(8):G781-93
references: 22241861
references: Anaerobe. 2005 Oct;11(5):247-51
references: 16701579
references: Mol Biol Cell. 2001 Oct;12(10):3031-45
references: 11598189
references: Int J Biochem Cell Biol. 2001 Jan;33(1):53-64
references: 11167132
references: J Mol Med (Berl). 2006 Dec;84(12):1055-66
references: 17058067
references: Blood. 2003 Dec 15;102(13):4336-44
references: 12881314
references: J Cell Sci. 2011 Dec 1;124(Pt 23):3933-40
references: 22194304
references: Trends Cell Biol. 2007 Aug;17(8):394-402
references: 17766116
references: BMC Gastroenterol. 2009 Jul 13;9:53
references: 19594939
references: Clin Cancer Res. 2011 May 15;17(10):3089-99
references: 21447726
references: Immunobiology. 2002 Mar;205(1):108-19
references: 11999340
references: Brain Res. 2006 Oct 9;1114(1):204-11
references: 16919610
references: Curr Protein Pept Sci. 2011 Dec;12(8):725-35
references: 22329548
references: Biochem Biophys Res Commun. 2006 Mar 31;342(1):236-44
references: 16480947