The Journal of Physiological Sciences

, Volume 66, Issue 1, pp 53–65 | Cite as

Effects of ezrin knockdown on the structure of gastric glandular epithelia

  • Saori Yoshida
  • Hiroto Yamamoto
  • Takahito Tetsui
  • Yuka Kobayakawa
  • Ryo Hatano
  • Ken-ichi Mukaisho
  • Takanori Hattori
  • Hiroyuki Sugihara
  • Shinji AsanoEmail author
Original Paper


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.


Ezrin 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.

Ethical approval

All work with animals was performed with the approval of the Animal Ethics Committees of Ritsumeikan University.

Supplementary material

12576_2015_393_MOESM1_ESM.pptm (49 kb)
Supplementary Fig. 1 mRNA expression levels of ezrin in the gastric corpus and pyloric antrum segments were compared between the wild-type and Vil2 kd/kd mice. The mRNA expression levels were normalized by the expression level of GAPDH, and the values were shown as the percentage to the expression levels in the wild-type. All data represent mean ± S.E. N=3 for wild-type and Vil2 kd/kd mice. **P < 0.01 versus wild-type. (PPTM 48 kb) (PPTM 48 kb)
12576_2015_393_MOESM2_ESM.pptm (570 kb)
Supplementary Fig. 2 Con A staining of the sections of gastric corpus of wild-type and Vil2 kd/kd mice. Sections of the gastric corpus of wild-type (a, c) and Vil2 kd/kd mice (b, d) were stained with H.E. (a, b) and Con A (c, d), respectively. Scale bar 100 µm. (PPTM 570 kb) (PPTM 570 kb)
12576_2015_393_MOESM3_ESM.pptm (501 kb)
Supplementary Fig. 3 Expression of ezrin and pepsin C in the gastric corpus segments. Immunofluoresence observation of the gastric corpus of wild-type and Vil2 kd/kd mice with the anti-ezrin (green) and anti-pepsin C antibodies (red), respectively at low (a) and high (b) magnifications. Immunofluoresence of the bottom part of gastric corpus was shown in (b). Scale bars 100 µm (b, c). (PPTM 501 kb) (PPTM 501 kb)
12576_2015_393_MOESM4_ESM.pptm (310 kb)
Supplementary Fig. 4 Expression of moesin in the gastric corpus segments of wild-type (a) and Vil2 kd/kd mice (b). The expression pattern of moesin was different from that of ezrin in the gastric corpus. In addition, moesin did not compensate the loss of ezrin in the Vil2 kd/kd parietal cells. Scale bar 100 µm. (PPTM 309 kb) (PPTM 309 kb)


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Copyright information

© The Physiological Society of Japan and Springer Japan 2015

Authors and Affiliations

  • Saori Yoshida
    • 1
  • Hiroto Yamamoto
    • 1
    • 2
  • Takahito Tetsui
    • 1
  • Yuka Kobayakawa
    • 1
  • Ryo Hatano
    • 1
  • Ken-ichi Mukaisho
    • 2
  • Takanori Hattori
    • 2
  • Hiroyuki Sugihara
    • 2
  • Shinji Asano
    • 1
    Email author
  1. 1.Department of Molecular Physiology, College of Pharmaceutical SciencesRitsumeikan UniversityKusatsuJapan
  2. 2.Department of PathologyShiga University of Medical SciencesOtsuJapan

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