Roles of COX-1 and COX-2 in gastrointestinal pathophysiology.
In this review, COX-1 and COX-2 proteins have been shown to be homologous in protein structure and ability to synthesize PG, but they have been also shown to be induced differently. COX-1 mRNA and protein have been shown to be induced slowly in intestinal crypt cells in response to irradiation and suggested to be important for crypt cell survival. Therefore, the cox-1 gene is suggested to be a delayed response gene in some systems. However, in cox-1 gene knockout animals there are no pathological gastric and intestinal findings. Although the precise roles of COX-1 in epithelial proliferation and differentiation in the gastrointestinal tract are not yet known, it apparently acts as a constitutive PG producer, thereby protecting the mucosa. On the other hand, COX-2 mRNA and protein have been shown to be induced rapidly in inflammatory sites of the stomach and colon. Thus, COX-2-derived PG presumably plays a role in the repair process of gastritis, ulcers, and colitis. Furthermore, loss of apc gene function probably induces COX-2 mRNA in gastrointestinal mucosa. Thus, high expression levels of COX-2 may lead to phenotypic changes in both intestinal epithelial cells and colon cancer cells.
Sakamoto
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Third Department of Internal Medicine, Nippon Medical School, Tokyo, Japan.
D003001:Cloning, Molecular; D005767:Gastrointestinal Diseases / Q000201:enzymology / Q000503:physiopathology*; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics / Q000378:metabolism*
D011451:Prostaglandin-Endoperoxide Synthases