Effects of ezrin knockdown on the structure of gastric glandular epithelia.
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.
Department of Molecular Physiology, College of Pharmaceutical Sciences, Ritsumeikan University, 1-1-1 Noji-Higashi, Kusatsu, Shiga, 525-8577, Japan.
Saori
S
Yoshida
Department of Molecular Physiology, College of Pharmaceutical Sciences, Ritsumeikan University, 1-1-1 Noji-Higashi, Kusatsu, Shiga, 525-8577, Japan.|Department of Pathology, Shiga University of Medical Sciences, Seta Tsukinowa-cho, Otsu, Shiga, 520-2192, Japan.
Hiroto
H
Yamamoto
Department of Molecular Physiology, College of Pharmaceutical Sciences, Ritsumeikan University, 1-1-1 Noji-Higashi, Kusatsu, Shiga, 525-8577, Japan.
Takahito
T
Tetsui
Department of Molecular Physiology, College of Pharmaceutical Sciences, Ritsumeikan University, 1-1-1 Noji-Higashi, Kusatsu, Shiga, 525-8577, Japan.
Yuka
Y
Kobayakawa
Department of Molecular Physiology, College of Pharmaceutical Sciences, Ritsumeikan University, 1-1-1 Noji-Higashi, Kusatsu, Shiga, 525-8577, Japan.
Ryo
R
Hatano
Department of Pathology, Shiga University of Medical Sciences, Seta Tsukinowa-cho, Otsu, Shiga, 520-2192, Japan.
Ken-ichi
K
Mukaisho
Department of Pathology, Shiga University of Medical Sciences, Seta Tsukinowa-cho, Otsu, Shiga, 520-2192, Japan.
Takanori
T
Hattori
Department of Pathology, Shiga University of Medical Sciences, Seta Tsukinowa-cho, Otsu, Shiga, 520-2192, Japan.
Hiroyuki
H
Sugihara
Department of Molecular Physiology, College of Pharmaceutical Sciences, Ritsumeikan University, 1-1-1 Noji-Higashi, Kusatsu, Shiga, 525-8577, Japan. ashinji@ph.ritsumei.ac.jp.
Shinji
S
Asano
D000126:Achlorhydria / Q000378:metabolism; D000818:Animals; D000906:Antibodies; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism*; D004848:Epithelium / Q000502:physiology*; D005753:Gastric Mucosa / Q000166:cytology / Q000502:physiology*; D005755:Gastrins / Q000097:blood; D005786:Gene Expression Regulation / Q000502:physiology*; D055785:Gene Knockdown Techniques; D037102:Lectins; D051379:Mice; D008822:Mice, Transgenic; D008856:Microscopy, Fluorescence; D055272:Mucin-6 / Q000235:genetics / Q000378:metabolism; D009077:Mucins / Q000235:genetics / Q000378:metabolism; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism; D010295:Parietal Cells, Gastric / Q000378:metabolism* / Q000648:ultrastructure; D010455:Peptides / Q000235:genetics / Q000378:metabolism; D012313:RNA / Q000235:genetics / Q000378:metabolism; D000071164:Trefoil Factor-2; D015854:Up-Regulation; D000099149:Ezrin
D000906:Antibodies; D003598:Cytoskeletal Proteins; D005755:Gastrins; D037102:Lectins; D055272:Mucin-6; D009077:Mucins; D009124:Muscle Proteins; D010455:Peptides; D012313:RNA; D000071164:Trefoil Factor-2; D000099149:Ezrin; C524735:Muc6 protein, mouse; C481546:TFF2 protein, mouse
Epithelium; Ezrin; Parietal cells; Secretory membrane