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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\u20101), the immediate early gene egr\u20101 and imbalance of angiogenic\/antiangiogenic molecules. Namely, we found an enhanced expression and release of ET\u20101 within 15\u201330 min after the administration of duodenal ulcerogen cysteamine, resulting in local ischemia that triggers the expression of hypoxia\u2010inducible factors (HIF\u20101\u03b1). Our gene expression studies also revealed an early (0.5\u20132 h) increase in the expression of egr\u20101 that is followed (12\u201324 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\u20101, egr\u20101 and angiogenesis\u2010related molecules.<\/jats:bold> <\/jats:p>","DOI":"10.1196\/annals.1391.033","type":"journal-article","created":{"date-parts":[[2007,10,31]],"date-time":"2007-10-31T20:43:53Z","timestamp":1193863433000},"page":"238-255","source":"Crossref","is-referenced-by-count":24,"title":["New Molecular Mechanisms of Duodenal Ulceration"],"prefix":"10.1111","volume":"1113","author":[{"given":"SANDOR","family":"SZABO","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"XIAOMING","family":"DENG","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"TETYANA","family":"KHOMENKO","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"LONGCHUAN","family":"CHEN","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"GANNA","family":"TOLSTANOVA","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"KLARA","family":"OSAPAY","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"ZSUZSANNA","family":"SANDOR","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"XIMING","family":"XIONG","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2007,11,5]]},"reference":[{"key":"e_1_2_6_2_2","first-page":"1","article-title":"Peptic ulcer disease","volume":"19","author":"Hunt R.H.","year":"1990","journal-title":"Gastroenterol. 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