title: Adenovirus-mediated hepatocarcinoma-intestine-pancreas/pancreatitis-associated protein suppresses dextran sulfate sodium-induced acute ulcerative colitis in rats.
abstract: BACKGROUND
  Although increased expression of hepatocarcinoma-intestine-pancreas/pancreatitis-associated protein (HIP/PAP) has been reported in ulcerative colitis (UC), its role in UC remains unclear. This study was designed to assess the function of HIP/PAP in experimental UC and further to explore its underlying mechanisms.
  
  
  METHODS
  Recombinant adenovirus was prepared to mediate ectopic expression of HIP/PAP in the colon of rats. The effect of HIP/PAP on dextran sodium sulfate (DSS)-induced colitis was assessed by disease activity index (DAI), macroscopic, and histological evaluations. Superoxide dismutase (SOD) and myeloperoxidase (MPO) activities, malondialdehyde (MDA) content, and tumor necrosis factor α (TNF-α) and interleukin-6 (IL-6) production were determined in colonic mucosa. Proliferation cell nuclear antigen (PCNA) was immunostained to reflect the proliferation of colonic epithelia. The effects of HIP/PAP on proliferation and H(2)O(2) -induced apoptosis of SW480 and LoVo colonic adenocarcinoma cells were also determined. Gene expression profiles in SW480 after HIP/PAP overexpression were analyzed by microarray analysis.
  
  
  RESULTS
  The protective effect of HIP/PAP against DSS-induced colitis in rats was confirmed. Ectopic expression of HIP/PAP resulted in attenuation of oxidative damage, reduction of TNF-α and IL-6 expression, and elevation of epithelial proliferation in colonic mucosa and led to decreased apoptosis and increased proliferation in colonic adenocarcinoma cells. Microarray analysis revealed altered expression of inflammation-related molecules, growth factors, proliferation-related molecules, and antioxidant enzymes under overexpression of HIP/PAP.
  
  
  CONCLUSIONS
  HIP/PAP has a protective effect against DSS-induced colitis in rats via inhibiting inflammation, alleviating oxidative damage, and promoting colonic epithelium regeneration. HIP/PAP might represent a new promising therapeutic strategy in UC.
authors.affiliation: Department of Gastroenterology, First Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an, China.
authors.forename: Yifei
authors.initials: Y
authors.lastname: Lv
authors.forename: Xiaofei
authors.initials: X
authors.lastname: Yang
authors.forename: Yongwei
authors.initials: Y
authors.lastname: Huo
authors.forename: Hong
authors.initials: H
authors.lastname: Tian
authors.forename: Shuang
authors.initials: S
authors.lastname: Li
authors.forename: Yan
authors.initials: Y
authors.lastname: Yin
authors.forename: Zhiming
authors.initials: Z
authors.lastname: Hao
mesh_terms: D000208:Acute Disease; D000230:Adenocarcinoma / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D000951:Antigens, Neoplasm / Q000235:genetics / Q000378:metabolism*; D017209:Apoptosis / Q000187:drug effects; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D015153:Blotting, Western; D049109:Cell Proliferation / Q000187:drug effects; D003093:Colitis, Ulcerative / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*; D003106:Colon / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D020869:Gene Expression Profiling; D006861:Hydrogen Peroxide / Q000494:pharmacology; D007124:Immunoenzyme Techniques; D007249:Inflammation / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D015850:Interleukin-6 / Q000378:metabolism; D007413:Intestinal Mucosa / Q000473:pathology*; D037181:Lectins, C-Type / Q000235:genetics / Q000378:metabolism*; D008315:Malondialdehyde / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D016877:Oxidants / Q000494:pharmacology; D018384:Oxidative Stress; D000073718:Pancreatitis-Associated Proteins; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D013482:Superoxide Dismutase / Q000378:metabolism; D014302:Trinitrobenzenesulfonic Acid / Q000633:toxicity*; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D015850:Interleukin-6; D037181:Lectins, C-Type; D016877:Oxidants; D000073718:Pancreatitis-Associated Proteins; C000612141:REG3A protein, human; C000612144:Reg3b protein, rat; D014409:Tumor Necrosis Factor-alpha; D008315:Malondialdehyde; D014302:Trinitrobenzenesulfonic Acid; D006861:Hydrogen Peroxide; D009195:Peroxidase; D013482:Superoxide Dismutase