Effects of ezrin knockdown on the structure of gastric glandular epithelia
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Ezrin, an adaptor protein that cross-links plasma membrane-associated proteins with the actin cytoskeleton, is concentrated on apical surfaces of epithelial cells, especially in microvilli of the small intestine and stomach. In the stomach, ezrin is predominantly expressed on the apical canalicular membrane of parietal cells. Transgenic ezrin knockdown mice in which the expression level of ezrin was reduced to <7 % compared with the wild-type suffered from achlorhydria because of impairment of membrane fusion between tubulovesicles and apical membranes. We observed, for the first time, hypergastrinemia and foveolar hyperplasia in the gastric fundic region of the knockdown mice. Dilation of fundic glands was observed, the percentage of parietal and chief cells was reduced, and that of mucous-secreting cells was increased. The parietal cells of knockdown mice contained dilated tubulovesicles and abnormal mitochondria, and subsets of these cells contained abnormal vacuoles and multilamellar structures. Therefore, lack of ezrin not only causes achlorhydria and hypergastrinemia but also changes the structure of gastric glands, with severe perturbation of the secretory membranes of parietal cells.
KeywordsEzrin Parietal cells Epithelium Secretory membrane
We thank Professor Tsukita for giving us the Vil2 kd/kd mice. We thank Dr Yosuke Matsumoto, Mr Hiroki Murakami, Ms Karin Ikeda, and Ms Kaori Akiyama for their help with breeding and genotyping of mice and for technical support. This research was supported in part by Grants-in-Aid for Scientific Research (21590082 and 24590104) from the Ministry of Education, Culture, Sports, Science and Technology of Japan to S.A., and a High-Tech Research Center Project for Private Universities: matching fund subsidy from the Ministry of Education, Culture, Sports, Science and Technology of Japan to S.A.
Compliance with ethical standards
Conflict of interest
The authors declare that there is no conflict of interest.
All work with animals was performed with the approval of the Animal Ethics Committees of Ritsumeikan University.
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