title: Activation of REG family proteins in colitis.
abstract: OBJECTIVE
  To do a genome-wide gene expression study of active and inactive ulcerative colitis and Crohn's disease (inflammatory bowel disease--IBD) and examine the most differentially expressed genes. As the study showed an extreme upregulation of all regenerating islet-derived genes (REG proteins) in active IBD, we further studied the expression of REGs on protein level in active and inactive IBD, as well as in non-IBD (pseudomembranous) colitis.
  
  
  METHODS
  Microarray analysis was done on a total of 100 pinch biopsy samples from healthy controls and patients with Crohn's disease or ulcerative colitis. Tissue samples from IBD and pseudomembranous colitis were examined with routine histology and immunohistochemical analysis for REGIα, REGIV, DEFA6, and serotonin.
  
  
  RESULTS
  REG mRNAs were up to 83 times overexpressed in diseased mucosa compared with mucosa from healthy individuals. REGIα and REGIV were overexpressed at immunohistochemistry and located to different mucosal cell types. REGIα was expressed in basal half of crypts, REGIV in mid and outer parts of crypts and in surface epithelium and seems to be stored in, and secreted from, goblets. Pseudomembranous colitis samples showed similar staining patterns, and some IBD samples stained REG positive without inflammation on routine histology.
  
  
  CONCLUSIONS
  All REG family mRNAs are upregulated in IBD. REGIα and REGIV have different cellular localization, possibly reflecting different biological functions. REG protein expression also in pseudomembranous colitis shows that REG family proteins are regulated in inflammatory injury and repair, not specifically for IBD as previously thought.
authors: Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway.
authors: Atle van Beelen
authors: Av
authors: Granlund
authors: Vidar
authors: V
authors: Beisvag
authors: Sverre H
authors: SH
authors: Torp
authors: Arnar
authors: A
authors: Flatberg
authors: Per Martin
authors: PM
authors: Kleveland
authors: Ann Elisabeth
authors: AE
authors: Ostvik
authors: Helge L
authors: HL
authors: Waldum
authors: Arne K
authors: AK
authors: Sandvik
mesh_terms: D003093:Colitis, Ulcerative / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D003424:Crohn Disease / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D004761:Enterocolitis, Pseudomembranous / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D015870:Gene Expression; D055106:Genome-Wide Association Study; D006801:Humans; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000737:chemistry; D037181:Lectins, C-Type / Q000032:analysis / Q000235:genetics*; D051847:Lithostathine / Q000032:analysis / Q000235:genetics*; D046228:Microarray Analysis; D000073718:Pancreatitis-Associated Proteins; D019879:Paneth Cells / Q000737:chemistry; D012333:RNA, Messenger / Q000032:analysis; D012701:Serotonin / Q000032:analysis; D015854:Up-Regulation; D023084:alpha-Defensins / Q000032:analysis / Q000235:genetics
chemical_list: C517765:DEFA6 protein, human; D037181:Lectins, C-Type; D051847:Lithostathine; D000073718:Pancreatitis-Associated Proteins; C428528:REG4 protein, human; D012333:RNA, Messenger; D023084:alpha-Defensins; D012701:Serotonin