Aoc3’ün İnflamatuar ve Neoplastik Kolon Hastalıklarındaki Rolünün Araştırılması

Abstract

The AOC3 gene is located on chromosome 17 and encodes the protein AOC3 (VAP-1), which is involved in leukocyte trafficking during inflammation. AOC3 is expressed by many different cell groups such as endothelium, adipocytes, pericytes, myofibroblasts and smooth muscle. AOC3 protein, which has two forms, membrane-bound and soluble, is also expressed by myofibroblasts, which are stromal cells in the gastrointestinal tract. The aim of this thesis was to investigate the effects of Aoc3 on the development of colitis and colorectal carcinogenesis in in vivo mouse disease models. In this context, firstly, the genotype of Aoc3 knockout mice obtained from Turku University, Finland was confirmed. In addition, the changes in Aoc3 expression in Aoc3 knockout and wild-type mice were compared. Secondly, the concentration of DSS to be used for Dextran Sulfate Sodium (DSS) colitis model was optimized. Third, an acute colitis model was established and it was observed that Aoc3 knockout mice were more prone to colitis than wild-type control mice. Fourth, Aoc3 knockout and wild-type mice were treated with Azoxymethane (AOM), DSS and AOM/DSS combination and their colons were examined for development of inflammation-induced colon cancer at the end of the follow-up period. However, AOM/DSS treatment significantly shortened the survival of Aoc3 mutant mice, but statistically significant results could not be obtained due to the decrease in the number of subjects. Fifth and finally, Apc+/- mutant mice were crossed with Aoc3 knockout mice and three groups of Apc+/- Aoc3+/+, Apc+/- Aoc3+/- and Apc+/- Aoc3-/- mice were followed up and it was found that there was a statistically significant increase in the number of colonic polyps in Apc+/- Aoc3-/- mice compared to Apc+/- Aoc3+/+ mice after sacrification. In conclusion, this study demonstrated that Aoc3 knockout mice are more susceptible to DSS-induced colitis and colonic tumorigenesis than wild-type mice in an in vivo disease model.