title: Peroxisome proliferator-activated receptor-γ is downregulated in ulcerative colitis and is involved in experimental colitis-associated neoplasia.
abstract: The aim of the present study was to evaluate the expression of peroxisome proliferator-activated receptor (PPAR)-γ in inflammatory bowel disease (IBD), and to also identify the association between PPAR-γ and the clinical features of patients with IBD. An azoxymethane (AOM)/dextran sodium sulfate (DSS) animal model of colitis-associated neoplasia was established to investigate the protective effect of 5-aminosalicylic acid (5-ASA) and to explore the changes in the expression of PPAR-γ during this process. A total of 66 specimens of colorectal tissue obtained from biopsy performed on IBD patients and 30 healthy control individuals were immunohistochemically stained for PPAR-γ. An AOM/DSS animal model of colitis-associated neoplasia was then established. Reverse transcription quantitative polymerase chain reaction was conducted and it was found that, compared with the control group and patients with Crohn's disease (CD), the expression of PPAR-γ in the intestinal tissue of patients with ulcerative colitis (UC) was significantly decreased (P=0.027 and 0.046, respectively). The expression of PPAR-γ was found to be negatively associated with the disease activity of UC and was not associated with the severity of disease, site of lesions or CD characteristics. Administration of 5-ASA decreased the colitis and tumor burden of colons. The expression level of PPAR-γ in the intestinal tissue was also increased in the AOM/DSS/5-ASA group compared with AOM/DSS group (P<0.001). PPAR-γ is an important factor in the pathogenesis of UC and colitis-associated cancer. The present study found that 5-ASA significantly alleviates the colitis and tumor burden in a mouse model of AOM/DSS-induced colitis-associated neoplasia, and promotes the expression of PPAR-γ in the intestinal tract.
authors.affiliation: Department of Gastroenterology, Nanjing Drum Tower Hospital, Nanjing University, Nanjing, Jiangsu 210000, P.R. China.
authors.forename: Xiaotan
authors.initials: X
authors.lastname: Dou
authors.affiliation: Department of Gastroenterology, Shanghai East Hospital, Tongji University, Shanghai 200085, P.R. China.
authors.forename: Junhua
authors.initials: J
authors.lastname: Xiao
authors.affiliation: Department of Oncology, Shanghai First People's Hospital, Shanghai Jiaotong University, Shanghai 200085, P.R. China.
authors.forename: Ziliang
authors.initials: Z
authors.lastname: Jin
authors.affiliation: Department of Gastroenterology, Shanghai East Hospital, Tongji University, Shanghai 200085, P.R. China.
authors.forename: Ping
authors.initials: P
authors.lastname: Zheng
keywords: 5-aminosalicylic acid; colonic neoplasms; peroxisome proliferator-activated receptor-γ; ulcerative colitis