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Pathogens 2013, 2(4), 571-590; doi:10.3390/pathogens2040571
Article

Effects of EGFR Inhibitor on Helicobacter pylori Induced Gastric Epithelial Pathology in Vivo

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Received: 13 August 2013; in revised form: 16 September 2013 / Accepted: 26 September 2013 / Published: 14 October 2013
(This article belongs to the Special Issue Gut Microbiome)
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Abstract: Helicobacter pylori transactivates the Epidermal Growth Factor Receptor (EGFR) and predisposes to gastric cancer development in humans and animal models. To examine the importance of EGFR signalling to gastric pathology, this study investigated whether treatment of Mongolian gerbils with a selective EGFR tyrosine kinase inhibitor, EKB-569, altered gastric pathology in chronic H. pylori infection. Gerbils were infected with H. pylori and six weeks later received either EKB-569-supplemented, or control diet, for 32 weeks prior to sacrifice. EKB-569-treated H. pylori-infected gerbils had no difference in H. pylori colonisation or inflammation scores compared to infected animals on control diet, but showed significantly less corpus atrophy, mucous metaplasia and submucosal glandular herniations along with markedly reduced antral and corpus epithelial proliferation to apoptosis ratios. EKB-569-treated infected gerbils had significantly decreased abundance of Cox-2, Adam17 and Egfr gastric transcripts relative to infected animals on control diet. EGFR inhibition by EKB-569 therefore reduced the severity of pre-neoplastic gastric pathology in chronically H. pylori-infected gerbils. EKB-569 increased gastric epithelial apoptosis in H. pylori-infected gerbils which counteracted some of the consequences of increased gastric epithelial cell proliferation. Similar chemopreventative strategies may be useful in humans who are at high risk of developing H.pylori-induced gastric adenocarcinoma.
Keywords: Helicobacter pylori; EGFR inhibitor; EKB-569; epithelial cell proliferation; apoptosis Helicobacter pylori; EGFR inhibitor; EKB-569; epithelial cell proliferation; apoptosis
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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MDPI and ACS Style

Crabtree, J.E.; Jeremy, A.H.; Duval, C.; Dixon, M.F.; Danjo, K.; Carr, I.M.; Pritchard, D.M.; Robinson, P.A. Effects of EGFR Inhibitor on Helicobacter pylori Induced Gastric Epithelial Pathology in Vivo. Pathogens 2013, 2, 571-590.

AMA Style

Crabtree JE, Jeremy AH, Duval C, Dixon MF, Danjo K, Carr IM, Pritchard DM, Robinson PA. Effects of EGFR Inhibitor on Helicobacter pylori Induced Gastric Epithelial Pathology in Vivo. Pathogens. 2013; 2(4):571-590.

Chicago/Turabian Style

Crabtree, Jean E.; Jeremy, Anthony H.; Duval, Cedric; Dixon, Michael F.; Danjo, Kazuma; Carr, Ian M.; Pritchard, D. M.; Robinson, Philip A. 2013. "Effects of EGFR Inhibitor on Helicobacter pylori Induced Gastric Epithelial Pathology in Vivo." Pathogens 2, no. 4: 571-590.



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