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  • Title: Adenovirus-mediated hepatocarcinoma-intestine-pancreas/pancreatitis-associated protein suppresses dextran sulfate sodium-induced acute ulcerative colitis in rats.
    Author: Lv Y, Yang X, Huo Y, Tian H, Li S, Yin Y, Hao Z.
    Journal: Inflamm Bowel Dis; 2012 Oct; 18(10):1950-60. PubMed ID: 22419609.
    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.
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