Increased expression of HIP/PAP and regenerating gene III in human inflammatory bowel disease and a murine bacterial reconstitution model.
Although microorganisms play a role in gut inflammation, it remains uncertain which epithelial genes are expressed in response to luminal flora and whether these molecules are also involved in pathologic mucosal inflammation. Germ-free mice were orally challenged with a bacterial suspension prepared from conventionally housed mice (bacterial reconstitution). Thereafter, the differential gene expression in gut epithelial cells was identified by differential display. The expression of the identified genes was also examined in dextran sulfate sodium (DSS)-induced colitis and human inflammatory bowel disease (IBD) epithelial cells. Regenerating gene III (Reg III) was strongly induced in gut epithelial cells following bacterial reconstitution, as well as in the colitis initiated by DSS. The mRNA expression of hepatocarcinoma-intestine-pancreas/pancreatic associated protein (HIP/PAP), a human counterpart of Reg III, was enhanced in colonic epithelial cells of patients with IBD. Reg III mRNA expression was localized in the epithelial cells including goblet cells and columnar cells in mice; on the other hand, HIP/PAP-expressing cells were correlated with Paneth cell metaplasia in human colon. Epithelial expression of Reg III or HIP/PAP was induced under mucosal inflammation initiated by exposure to commensal bacteria or DSS as well as inflamed IBD colon.
Ogawa
Hitoshi
H
Department of Surgery, Tohoku University Graduate School of Medicine, Sendai, Japan. hogawa@mcw.edu
Fukushima
Kouhei
K
Naito
Hiroo
H
Funayama
Yuji
Y
Unno
Michiaki
M
Takahashi
Ken-ichi
K
Kitayama
Taku
T
Matsuno
Seiki
S
Ohtani
Haruo
H
Takasawa
Shin
S
Okamoto
Hiroshi
H
Sasaki
Iwao
I
D000818:Animals; D000951:Antigens, Neoplasm / Q000235:genetics*; D014408:Biomarkers, Tumor / Q000235:genetics*; D015152:Blotting, Northern; D003093:Colitis, Ulcerative / Q000139:chemically induced / Q000473:pathology; D003424:Crohn Disease / Q000473:pathology; D004755:Enterobacteriaceae / Q000276:immunology*; D004847:Epithelial Cells / Q000378:metabolism; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D005809:Genes, Regulator / Q000235:genetics*; D015212:Inflammatory Bowel Diseases / Q000235:genetics / Q000276:immunology / Q000382:microbiology* / Q000473:pathology; D037181:Lectins, C-Type / Q000235:genetics*; D051379:Mice; D008813:Mice, Inbred ICR; D000073718:Pancreatitis-Associated Proteins; D016133:Polymerase Chain Reaction; D011506:Proteins; D012333:RNA, Messenger / Q000378:metabolism; D013047:Specific Pathogen-Free Organisms
D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D037181:Lectins, C-Type; D000073718:Pancreatitis-Associated Proteins; D011506:Proteins; C000612141:REG3A protein, human; D012333:RNA, Messenger; C490253:Reg3b protein, mouse