title: DMBT1 confers mucosal protection in vivo and a deletion variant is associated with Crohn's disease.
abstract: OBJECTIVE
  Impaired mucosal defense plays an important role in the pathogenesis of Crohn's disease (CD), one of the main subtypes of inflammatory bowel disease (IBD). Deleted in malignant brain tumors 1 (DMBT1) is a secreted scavenger receptor cysteine-rich protein with predominant expression in the intestine and has been proposed to exert possible functions in regenerative processes and pathogen defense. Here, we aimed at analyzing the role of DMBT1 in IBD.
  
  
  METHODS
  We studied DMBT1 expression in IBD and normal tissues by quantitative reverse transcription-polymerase chain reaction, immunohistochemistry, and mRNA in situ hybridization. Genetic polymorphisms within DMBT1 were analyzed in an Italian IBD case-control sample. Dmbt1(-/-) mice were generated, characterized, and analyzed for their susceptibility to dextran sulfate sodium-induced colitis.
  
  
  RESULTS
  DMBT1 levels correlate with disease activity in inflamed IBD tissues. A highly significant fraction of the patients with IBD displayed up-regulation of DMBT1 specifically in the intestinal epithelial surface cells and Paneth cells. A deletion allele of DMBT1 with a reduced number of scavenger receptor cysteine-rich domain coding exons is associated with an increased risk of CD (P = .00056; odds ratio, 1.75) but not for ulcerative colitis. Dmbt1(-/-) mice display enhanced susceptibility to dextran sulfate sodium-induced colitis and elevated Tnf, Il6, and Nod2 expression levels during inflammation.
  
  
  CONCLUSIONS
  DMBT1 may play a role in intestinal mucosal protection and prevention of inflammation. Impaired DMBT1 function may contribute to the pathogenesis of CD.
authors.affiliation: Division of Molecular Genome Analysis, Deutsches Krebsforschungszentrum, Heidelberg, Germany.
authors.forename: Marcus
authors.initials: M
authors.lastname: Renner
authors.forename: Gaby
authors.initials: G
authors.lastname: Bergmann
authors.forename: Inge
authors.initials: I
authors.lastname: Krebs
authors.forename: Caroline
authors.initials: C
authors.lastname: End
authors.forename: Stefan
authors.initials: S
authors.lastname: Lyer
authors.forename: Frank
authors.initials: F
authors.lastname: Hilberg
authors.forename: Burkhard
authors.initials: B
authors.lastname: Helmke
authors.forename: Nikolaus
authors.initials: N
authors.lastname: Gassler
authors.forename: Frank
authors.initials: F
authors.lastname: Autschbach
authors.forename: Floris
authors.initials: F
authors.lastname: Bikker
authors.forename: Olga
authors.initials: O
authors.lastname: Strobel-Freidekind
authors.forename: Sabine
authors.initials: S
authors.lastname: Gronert-Sum
authors.forename: Axel
authors.initials: A
authors.lastname: Benner
authors.forename: Stephanie
authors.initials: S
authors.lastname: Blaich
authors.forename: Rainer
authors.initials: R
authors.lastname: Wittig
authors.forename: Melanie
authors.initials: M
authors.lastname: Hudler
authors.forename: Antoon J
authors.initials: AJ
authors.lastname: Ligtenberg
authors.forename: Jens
authors.initials: J
authors.lastname: Madsen
authors.forename: Uffe
authors.initials: U
authors.lastname: Holmskov
authors.forename: Vito
authors.initials: V
authors.lastname: Annese
authors.forename: Anna
authors.initials: A
authors.lastname: Latiano
authors.forename: Peter
authors.initials: P
authors.lastname: Schirmacher
authors.forename: Arie V Nieuw
authors.initials: AV
authors.lastname: Amerongen
authors.forename: Mauro
authors.initials: M
authors.lastname: D'Amato
authors.forename: Petra
authors.initials: P
authors.lastname: Kioschis
authors.forename: Mathias
authors.initials: M
authors.lastname: Hafner
authors.forename: Annemarie
authors.initials: A
authors.lastname: Poustka
authors.forename: Jan
authors.initials: J
authors.lastname: Mollenhauer
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D002135:Calcium-Binding Proteins; D016022:Case-Control Studies; D002648:Child; D003424:Crohn Disease / Q000139:chemically induced / Q000235:genetics* / Q000503:physiopathology*; D004268:DNA-Binding Proteins; D016264:Dextran Sulfate; D004198:Disease Susceptibility; D005091:Exons / Q000235:genetics; D005260:Female; D017353:Gene Deletion; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D008875:Middle Aged; D009077:Mucins / Q000235:genetics / Q000502:physiology; D053473:Nod2 Signaling Adaptor Protein / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000235:genetics* / Q000502:physiology*; D012307:Risk Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D025521:Tumor Suppressor Proteins; D015854:Up-Regulation / Q000235:genetics
chemical_list: D002135:Calcium-Binding Proteins; C108174:DMBT1 protein, human; D004268:DNA-Binding Proteins; C114202:Dmbt1 protein, mouse; D015850:Interleukin-6; D009077:Mucins; D053473:Nod2 Signaling Adaptor Protein; C495945:Nod2 protein, mouse; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D014409:Tumor Necrosis Factor-alpha; D025521:Tumor Suppressor Proteins; D016264:Dextran Sulfate