bak deletion stimulates gastric epithelial proliferation and enhances Helicobacter felis-induced gastric atrophy and dysplasia in mice.

Autor:	Duckworth CA; Department of Gastroenterology, Institute of Translational Medicine, University of Liverpool, Liverpool, United Kingdom;, Abuderman AA; Department of Gastroenterology, Institute of Translational Medicine, University of Liverpool, Liverpool, United Kingdom;, Burkitt MD; Department of Gastroenterology, Institute of Translational Medicine, University of Liverpool, Liverpool, United Kingdom;, Williams JM; Department of Gastroenterology, Institute of Translational Medicine, University of Liverpool, Liverpool, United Kingdom;, O'Reilly LA; The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia; and Department of Medical Biology, The University of Melbourne, Parkville, Victoria, Australia., Pritchard DM; Department of Gastroenterology, Institute of Translational Medicine, University of Liverpool, Liverpool, United Kingdom; mark.pritchard@liverpool.ac.uk.
Jazyk:	angličtina
Zdroj:	American journal of physiology. Gastrointestinal and liver physiology [Am J Physiol Gastrointest Liver Physiol] 2015 Sep 15; Vol. 309 (6), pp. G420-30. Date of Electronic Publication: 2015 Jul 09.
DOI:	10.1152/ajpgi.00404.2014
Abstrakt:	Helicobacter infection causes a chronic superficial gastritis that in some cases progresses via atrophic gastritis to adenocarcinoma. Proapoptotic bak has been shown to regulate radiation-induced apoptosis in the stomach and colon and also susceptibility to colorectal carcinogenesis in vivo. Therefore we investigated the gastric mucosal pathology following H. felis infection in bak-null mice at 6 or 48 wk postinfection. Primary gastric gland culture from bak-null mice was also used to assess the effects of bak deletion on IFN-γ-, TNF-α-, or IL-1β-induced apoptosis. bak-null gastric corpus glands were longer, had increased epithelial Ki-67 expression, and contained fewer parietal and enteroendocrine cells compared with the wild type (wt). In wt mice, bak was expressed at the luminal surface of gastric corpus glands, and this increased 2 wk post-H. felis infection. Apoptotic cell numbers were decreased in bak-null corpus 6 and 48 wk following infection and in primary gland cultures following cytokine administration. Increased gastric epithelial Ki-67 labeling index was observed in C57BL/6 mice after H. felis infection, whereas no such increase was detected in bak-null mice. More severe gastric atrophy was observed in bak-null compared with C57BL/6 mice 6 and 48 wk postinfection, and 76% of bak-null compared with 25% of C57BL/6 mice showed evidence of gastric dysplasia following long-term infection. Collectively, bak therefore regulates gastric epithelial cell apoptosis, proliferation, differentiation, mucosal thickness, and susceptibility to gastric atrophy and dysplasia following H. felis infection. (Copyright © 2015 the American Physiological Society.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu