Reg gene expression is increased in rat gastric enterochromaffin-like cells following water immersion stress

Asahara, Masahiro; Mushiake, Sotaro; Shinji, Seiichi; Fukui, Hiroshi; Kinoshita, Yoshikazu; Kawanami, Chiharu; Watanabe, Tsuyoshi; Tanaka, Shinwa; Ichikawa, Ayako; Uchiyama, Yoshiyasu; Narushima, Yoichi; Takasawa, Shin; Okamoto, Hiroshi; Tohyama, Masaya; Chiba, Tsutomu

doi:10.1053/gast.1996.v111.pm8698224

Cited by 111 publications

(98 citation statements)

References 6 publications

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“…Four hours after exposure to aspirin in rats, we found the number of cells expressing RegI increases specifically in areas close to injury sites, in keeping with the findings of others (Asahara et al, 1996;Kawanami et al, 1997). Once adaptation is established, the number of RegIexpressing cells, and also the level of expression, is increased not only in areas that are injured but also throughout the mucosa in areas that appear macroscopically normal but are likely healing from earlier injury.…”

Section: Discussionsupporting

confidence: 90%

“…It has been clearly demonstrated that RegI is expressed only in endocrine cells, mostly enterochromaffin-like (ECL) cells, in normal and injured rat stomach (Asahara et al, 1996). Four hours after exposure to aspirin in rats, we found the number of cells expressing RegI increases specifically in areas close to injury sites, in keeping with the findings of others (Asahara et al, 1996;Kawanami et al, 1997).…”

Section: Discussionsupporting

confidence: 88%

“…RegI expression has been shown to increase up to 10-fold after a single high dose of indomethacin or after acute water immersion restraint stress (Asahara et al, 1996;Kawanami et al, 1997). In contrast, RegI was not significantly increased in the mucosa after the first aspirin dose in our experiments, although focal increases in expression at sites of injury were observed.…”

Section: Alderman Et Alcontrasting

confidence: 74%

“…RegI was first isolated in 1988 (Terazono et al, 1988) and, although much of the research to date has been concentrated on its role in the pancreas, it has also been shown to be expressed in normal stomach (Watanabe et al, 1990) and to increase after acute gastric mucosal injury (Asahara et al, 1996;Kawanami et al, 1997). In keeping with its mitogenic role in regenerating pancreatic islets, it has been suggested that RegI facilitates normal proliferation in the gastric epithelium and may also augment the proliferation of gastric epithelial cells after injury.…”

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confidence: 99%

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Insights into the Mechanisms of Gastric Adaptation to Aspirin-Induced Injury: A Role for Regenerating Protein but Not Trefoil Peptides

Alderman

Ulaganathan

Judd

et al. 2003

Laboratory Investigation

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SUMMARY:The phenomenon of reduced gastric mucosal injury despite repeated doses of a damaging agent is termed adaptation. Adaptation to nonsteroidal anti-inflammatory drug-induced injury has been clearly demonstrated in both humans and experimental animals; however, the precise mechanisms remain unclear. We hypothesized that mediators of adaptation might be the regenerating protein (RegI) and the trefoil peptides TFF1 and TFF2, because these proteins play pivotal roles in gastric mucosal protection and repair. The gene expression and the protein levels of these proteins were measured and compared in normal, aspirin-injured, and aspirin-adapted rat stomachs. TFF gene and protein expression levels were similar in all three groups, whereas RegI gene expression and protein levels in adapted stomach were increased. A time course analysis of RegI expression during the onset and offset of adaptation showed that mucosal RegI increased during the development of adaptation, was maintained during subsequent aspirin dosing, and returned to baseline levels once dosing had ceased and adaptation was lost-indicative of a causal role in the adaptation process. Colocalization of increased RegI with gastric epithelial areas showing increased proliferation also suggests that RegI may be an important mediator of the resolution of mucosal injury that is characteristic of gastric adaptation to aspirin. (Lab Invest 2003, 83:1415-1425.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionsupporting

confidence: 88%

Section: Alderman Et Alcontrasting

confidence: 74%

mentioning

confidence: 99%

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Insights into the Mechanisms of Gastric Adaptation to Aspirin-Induced Injury: A Role for Regenerating Protein but Not Trefoil Peptides

Alderman

Ulaganathan

Judd

et al. 2003

Laboratory Investigation

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“…In addition to the role of Reg I in the pancreas, we have demonstrated that Reg I functions as a growth factor in gastric cells and is involved in gastric mucosal regeneration (Asahara et al, 1996;Fukui et al, 1998;Kazumori et al, 2000). Recently, we generated Reg I-transgenic mice, which showed that Reg I is a key regulatory molecule for the maintenance of the growth axis of the gastric glands (Miyaoka et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

Reg I-knockout mice reveal its role in regulation of cell growth that is required in generation and maintenance of the villous structure of small intestine

et al. 2006

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Reg I (regenerating gene product I) is a growth factor that plays a central role in the generation and regeneration of the gastric mucosal architecture. On the other hand, mouse Reg I mRNA is expressed at the highest levels in the small intestine among the gastrointestinal tissues. In the current study, with the aim to clarify the role of Reg I protein in the small intestine, the temporal and spatial pattern of Reg I expression and the phenotype of Reg I-knockout mice in the tissue were examined. In the wild-type mice, immunohistochemistry localized Reg I protein expression in absorptive cells located in the lower half of the intestinal villi. Reg I expression was undetectable until embryonic day 13 (E13), when the fetal intestine still lacks villous structure; however, it dramatically increased at E17 along with the formation and maturation of the fetal intestinal villi. In the small intestine of the adult Reg I-knockout mice, less densely packed, round-shaped aberrant morphology of the absorptive cells was observed light microscopically, and electron microscopical examination revealed a strikingly loose connection of these cells to the basement membrane. Antiproliferating cell nuclear antigen staining and anti-Ki67 staining demonstrated the marked decrease in the number of proliferating cells in the small intestinal mucosa of the knockout mice. The cell migration speed visualized by one shot labeling of 5-bromodeoxyuridine was significantly slower in the knockout mice. These phenotypes of Reg I-knockout mice emerged, in accordance with the temporal pattern of Reg I expression described above, from E17. Reg I was considered to be a regulator of cell growth that is required to generate and maintain the villous structure of the small intestine.

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Classification of gastric endocrine cells at the light and electron microscopical levels

Bordi

D’Adda

Azzoni

et al. 2000

Microsc. Res. Tech.

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This review discusses the current concepts for the classification of gastric endocrine cells subdivided according to the type of mucosa in which they are located. In the oxyntic mucosa, the most important cell type is the ECL cell, involved in the synthesis and secretion of histamine. Proteins involved in many aspects of the biology of ECL cells including the response to the gastrin stimulus, membrane transport and docking, prevention of apoptosis, calcium homeostasis, autocrine activity, and maintenance of the differentiated cell phenotype have been localized to this cell type. Other cells of the oxyntic mucosa include: the D and EC cells producing somatostatin and serotonin, respectively, delivered through long cell processes; the X (or A‐like) cells, possibly producing endothelin; and the D1 and P cells of unknown function and possibly representing morphological variants of other cell types. In the antral mucosa, the three important cell types are represented by: the gastrin‐producing G cells; the somatostatin‐producing D cells, which are anatomically and functionally associated with G cells; and the serotonin‐producing EC cells, which are located at the bottom of antral glands. Microsc. Res. Tech. 48:258–271, 2000 © 2000 Wiley‐Liss, Inc.

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Reg gene expression is increased in rat gastric enterochromaffin-like cells following water immersion stress

Cited by 111 publications

References 6 publications

Insights into the Mechanisms of Gastric Adaptation to Aspirin-Induced Injury: A Role for Regenerating Protein but Not Trefoil Peptides

Insights into the Mechanisms of Gastric Adaptation to Aspirin-Induced Injury: A Role for Regenerating Protein but Not Trefoil Peptides

Reg I-knockout mice reveal its role in regulation of cell growth that is required in generation and maintenance of the villous structure of small intestine

Classification of gastric endocrine cells at the light and electron microscopical levels

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