title: Transgenic overexpression of Reg protein caused gastric cell proliferation and differentiation along parietal cell and chief cell lineages.
abstract: Reg (regenerating gene product) was originally identified as a growth factor involved in pancreatic regeneration. During the healing course of gastric erosion, Reg expression is highly increased in the enterochromaffin-like (ECL) cells surrounding the ulcer crater, suggesting its role as a regulator of gastric mucosal regeneration. However, there has been no direct in vivo evidence of a growth-promoting role of Reg for the gastric mucosal cells. In the current study, Reg-transgenic mice were created and gastric mucosa were analysed for histological changes. Transgenic mice showed a marked increase in the thickness of the fundic mucosa. Anti-proliferating cell nuclear antigen (PCNA) staining of the fundic mucosa demonstrated the enlargement of the proliferating neck zone and the lower PCNA-negative zone. Histological analysis employing antibodies against cell-type markers revealed expansion of the chief cell and parietal cell populations and no change in the number of surface mucus-producing cells, ECL cells, or G cells. In conclusion, Reg has a growth-promoting effect on gastric progenitor cells and an activity to direct the differentiation of the cells into chief cell and parietal cell lineages. This was in contrast to other factors, all of which had been shown to drive differentiation towards mucus producing cells in vivo. In the injured gastric mucosa, Reg may play a unique and important part in the reconstruction of the properly organized mucosal architecture.
authors.affiliation: Second Department of Internal Medicine, Shimane Medical University, Izumo 693-8501, Japan.
authors.forename: Youichi
authors.initials: Y
authors.lastname: Miyaoka
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Kadowaki
authors.forename: Shunji
authors.initials: S
authors.lastname: Ishihara
authors.forename: Takayuki
authors.initials: T
authors.lastname: Ose
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Fukuhara
authors.forename: Hideaki
authors.initials: H
authors.lastname: Kazumori
authors.forename: Shin
authors.initials: S
authors.lastname: Takasawa
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Okamoto
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Chiba
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Kinoshita
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology; D002135:Calcium-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology*; D002455:Cell Division / Q000502:physiology; D019872:Chief Cells, Gastric / Q000502:physiology*; D005753:Gastric Mucosa / Q000166:cytology / Q000254:growth & development / Q000473:pathology; D006023:Glycoproteins / Q000235:genetics* / Q000378:metabolism; D051847:Lithostathine; D051379:Mice; D008822:Mice, Transgenic; D010295:Parietal Cells, Gastric / Q000502:physiology*
chemical_list: D002135:Calcium-Binding Proteins; D006023:Glycoproteins; D051847:Lithostathine; C497615:Reg1 protein, mouse