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Overexpression of cyclin‐dependent kinase (CDK) inhibitors p21 and p27 is a common mechanism of experimental duodenal ulcer and ulcerative colitis
Author(s) -
Paunovic Brankica,
Khomenko Tetyana,
Deng Xiaoming,
Xiong Ximing,
Sandor Zsuzsanna,
Szabo Sandor
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.1027.4
Subject(s) - cysteamine , duodenum , ulcerative colitis , medicine , pathogenesis , iodoacetamide , colitis , chemistry , gastroenterology , cancer research , enzyme , biochemistry , disease , cysteine
Recently we demonstrated that increased expression of cyclin‐dependent kinase inhibitors p21 and p27 is an early event in duodenal ulceration (DU) induced by cysteamine or mepirizole and in indomethacin‐caused gastric erosions. We hypothesized that overexpression of p21, p27 and p16 may be involved in the mechanisms of mucosal damage in both DU and ulcerative colitis (UC). To compare the effect of chemically‐induced injury in duodenal and colonic mucosa, Sprague‐Dawley rats were treated with cysteamine (85 mg/100 g, intragastrically) or with 6% iodoacetamide (0.1 ml, intracolonically). Animals were euthanized at 0.5, 2, 6, 12, 24 hr after treatment. Mucosal scrapings of proximal duodenum and distal colon were used for RNA isolation; p16, p21 and p27 were detected by Real‐time polymerase chain reaction. The results demonstrated that cysteamine enhanced duodenal p21 and p27 mRNA expression at 2 hr by 2.9‐ and 4.6‐fold, respectively. In colonic mucosa iodoacetamide increased p21 by 4.2‐fold and p27 expression by 1.5‐fold. Expression of p16 changed in neither DU nor UC. Conclusions 1) Expressions of p21 and p27 were significantly increased in rat duodenal and colonic mucosa in the early stages of DU and UC formation. 2) Thus, both p21 and p27 but not p16 seem to be a common mechanism involved in the pathogenesis of DU and UC. (This study was supported by Dept of Veterans Affairs, Medical Research Service Merit Reviews)