caa a22 4500 445889020 CHVBK 20180317145609.0 cr unu---uuuuu 170323e20110501xx s 000 0 eng 10.1007/s00535-011-0391-0 doi (NATIONALLICENCE)springer-10.1007/s00535-011-0391-0 Cell lineage dynamics in the process leading to intestinal metaplasia [Elektronische Daten] [Hirotsugu Sakamoto, Hiroyuki Mutoh, Hiroko Hayakawa, Miho Sashikawa, Kentaro Sugano] Background: Gene expression in the early stage of the transition to intestinal metaplasia in human gastric mucosa has not been determined. In this study, we investigated the temporal relationship between cell lineage changes and intestine-specific gene expression in the process leading to intestinal metaplasia, using Cdx2-transgenic mice. Methods: Cellular phenotypes were analyzed by immunohistochemistry and were compared with the gene expression profiles of cell lineage markers by real-time polymerase chain reaction. Results: Up to postnatal day (PD) 20, the gastric mucosae of Cdx2-transgenic mice were histologically similar to those of their normal littermates. However, at approximately PD 20, we observed the sporadic appearance of glands in which all the epithelial cells expressed Cdx2 (Cdx2-diffuse positive glands). In the Cdx2-diffuse positive glands, parietal cells had disappeared, the proliferating zone had moved from the isthmus to the base, and absorptive cells and goblet cells were recognized. In contrast, the surrounding mucosa retained the phenotype of the gastric gland in which only some of the epithelial cells expressed Cdx2. During PDs 30 and 40, the entire fundic mucosa changed to transdifferentiated mucosa that was a composite of intestinal metaplasia and spasmolytic polypeptide-expressing metaplasia. An increase in the expression of intestine-specific genes, with a reciprocal decrease in gastric-specific gene expression, began much earlier than the emergence of Cdx2-diffuse positive glands. Conclusions: A dramatic increase in intestine-specific gene expression precedes the morphological appearance of intestinal metaplasia and spasmolytic polypeptide-expressing metaplasia. Springer, 2011 Cdx2 nationallicence Intestinal metaplasia nationallicence Spasmolytic polypeptide-expressing metaplasia nationallicence Transgenic mouse nationallicence Sakamoto Hirotsugu Division of Gastroenterology, Department of Medicine, Jichi Medical University, 3311-1 Yakushiji, 329-0498, Shimotsuke, Tochigi, Japan aut Mutoh Hiroyuki Division of Gastroenterology, Department of Medicine, Jichi Medical University, 3311-1 Yakushiji, 329-0498, Shimotsuke, Tochigi, Japan aut Hayakawa Hiroko Division of Gastroenterology, Department of Medicine, Jichi Medical University, 3311-1 Yakushiji, 329-0498, Shimotsuke, Tochigi, Japan aut Sashikawa Miho Division of Gastroenterology, Department of Medicine, Jichi Medical University, 3311-1 Yakushiji, 329-0498, Shimotsuke, Tochigi, Japan aut Sugano Kentaro Division of Gastroenterology, Department of Medicine, Jichi Medical University, 3311-1 Yakushiji, 329-0498, Shimotsuke, Tochigi, Japan aut Journal of Gastroenterology Springer Japan 46/5(2011-05-01), 620-628 0944-1174 46:5<620 2011 46 535 https://doi.org/10.1007/s00535-011-0391-0 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s00535-011-0391-0 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Sakamoto Hirotsugu Division of Gastroenterology, Department of Medicine, Jichi Medical University, 3311-1 Yakushiji, 329-0498, Shimotsuke, Tochigi, Japan aut NATIONALLICENCE 700 1- Mutoh Hiroyuki Division of Gastroenterology, Department of Medicine, Jichi Medical University, 3311-1 Yakushiji, 329-0498, Shimotsuke, Tochigi, Japan aut NATIONALLICENCE 700 1- Hayakawa Hiroko Division of Gastroenterology, Department of Medicine, Jichi Medical University, 3311-1 Yakushiji, 329-0498, Shimotsuke, Tochigi, Japan aut NATIONALLICENCE 700 1- Sashikawa Miho Division of Gastroenterology, Department of Medicine, Jichi Medical University, 3311-1 Yakushiji, 329-0498, Shimotsuke, Tochigi, Japan aut NATIONALLICENCE 700 1- Sugano Kentaro Division of Gastroenterology, Department of Medicine, Jichi Medical University, 3311-1 Yakushiji, 329-0498, Shimotsuke, Tochigi, Japan aut NATIONALLICENCE 773 0- Journal of Gastroenterology Springer Japan 46/5(2011-05-01), 620-628 0944-1174 46:5<620 2011 46 535 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer