Параметри
New molecular mechanisms of duodenal ulceration
Журнал :
Annals of the New York Academy of Sciences
Том :
1113
Випуск :
1
ISSN :
0077-8923
Початкова сторінка :
238
Кінцева сторінка :
255
Дата випуску :
1 січня 2007 р.
Автор(и) :
Szabo, Sandor
Deng, Xiaoming
Khomenko, Tetyana
Chen, Longchuan
Taras Shevchenko National University of Kyiv
Osapay, Klara
Sandor, Zsuzsanna
Xiong, Ximing
Анотація :
Stress is a major etiologic factor in the pathogenesis of gastric and duodenal ulceration, as first described in rats by Hans Selye. In patients with "peptic ulcers" duodenal ulcers are more frequent than gastric ulcers (except in Japan). Thus, our research during the last three decades focused on the molecular mechanisms of duodenal ulcer in rodent models of chemically induced duodenal ulceration, and here we review our three recent findings: Endothelins (ET-1), the immediate early gene egr-1 and imbalance of angiogenic/antiangiogenic molecules. Namely,we found an enhanced expression and release of ET-1 within 15-30 min after the administration of duodenal ulcerogen cysteamine, resulting in local ischemia that triggers the expression of hypoxia-inducible factors (HIF-1α). Our gene expression studies also revealed an early (0.5-2 h) increase in the expression of egr-1 that is followed (12-24 h) by upregulation of angiogenic growth factors (e.g., VEGF, bFGF, PDGF). Surprisingly, this event is also associated with an enhanced production of angiostatin and endostatin that probably counteract the beneficial effect of angiogenic molecules. Thus, the initial injury to endothelial and epithelial cells in duodenal ulceration seems to be aggravated (and not initiated) by HCl and proteolytic enzymes. The resulting mucosal necrosis does not rapidly heal because of the imbalance of VEGF and angiostatin/endostatin, hence duodenal ulcers develop. The experimental ulcers Selye described morphologically are now characterized at the molecular and genome level, involving unexpected mediators like ET-1, egr-1 and angiogenesis-related molecules. © 2007 New York Academy of Sciences.