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 H2O2-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. (Inflamm Bowel Dis 2012) Copyright © 2012 Crohn's & Colitis Foundation of America, Inc.