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Expression of extracellular matrix proteins in the fetal rat gastric mucosa
Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
Department of Cell Biology and Biochemistry, AstraZeneca R&D, Mölndal, Sweden.
Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
2000 (English)In: Anatomy and Embryology, ISSN 0340-2061, E-ISSN 1432-0568, Vol. 201, no 3, 149-156 p.Article in journal (Refereed) Published
Abstract [en]

At gestational day 16 the epithelium of the rat stomach consists of a stratified layer of undifferentiated cells, and two days later glandular structures appear. The present study was carried out to identify extracellular matrix proteins that could be involved in the epithelial cell proliferation and differentiation processes that occur in the fetal rat stomach during this period. For comparative purposes the expression of the same components in the adult gastric mucosa was examined. Pregnant Sprague-Dawley rats received an intraperitoneal injection of 5-bromo-2’-deoxyuridine to label proliferating cells. One, 3.5, or 6 h post-injection the stomachs were excised and immediately frozen. The specimens were sectioned and stained with hematoxylin and eosin or for 5-bromo-2’-deoxyuridine, cytokeratin no. 8, H,K-ATPase, and the extracellular matrix proteins fibronectin, laminin, and collagens type I and IV. A stratified layer of proliferating cells was observed in the epithelium of the fetal stomachs, while in adult stomachs proliferating cells were detected in the isthmus/neck region of the glands. Cytokeratin, an epithelial cell marker, was sparse at gestational day 16 but abundant both at gestational day 18 and in the isthmus/neck region of gastric glands of the adult stomach. The parietal cell marker H,K-ATPase could not be detected in the fetal stomachs during this period. Fibronectin was observed in the stroma of both fetal and adult stomachs. Collagen type I could only be detected in the stroma close to the oesophagus at gestational day 16. Two days later, collagen type I was abundant in the lamina propria, the submucosa and in the serosa of the fetal stomachs. In adult tissue collagen type I was detected in the surface epithelium, the submucosa and in the serosa of the stomach. Collagen type IV and laminin were expressed in the lamina propria, the basement membranes around blood vessels, muscle cells, and nerve bundles, as well as in the serosa of both 16- and 18-day-old fetal and adult rat stomachs. In conclusion, a high cell proliferation rate was observed in the epithelium at both gestational days 16 and 18. The increased expression of cytokeratin observed during this period indicates that the epithelial character of the embryonic cells becomes more distinct, while the remarkable change in the expression of collagen type I might reflect an important role of collagen type I in the development of the gastric epithelium.

Place, publisher, year, edition, pages
2000. Vol. 201, no 3, 149-156 p.
Keyword [en]
Cell differentiation, Cell proliferation, Collagen, Fetal development, Fibronectin, Immunohistochemistry, Keratin, Laminin
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:liu:diva-25282DOI: 10.1007/PL00008236Local ID: 9722OAI: oai:DiVA.org:liu-25282DiVA: diva2:245610
Available from: 2009-10-07 Created: 2009-10-07 Last updated: 2017-12-13Bibliographically approved
In thesis
1. The role of gastrin and extracellular matrix proteins in proliferation and differentiation of gastric epithelial cells
Open this publication in new window or tab >>The role of gastrin and extracellular matrix proteins in proliferation and differentiation of gastric epithelial cells
2000 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The mechanisms regulating the proliferation and differentiation processes that give rise to and maintain the gastric epithelium have not yet been completely elucidated.

In the present studies, in vitro models were established and the influence of growth factors and extracellular matrix proteins on these processes were investigated. Pentagastrin and hydrocortisone were found to accelerate the development of H,KTPase-positive parietal cells and other epithelial cells from undifferentiated gastric epithelial cells of foetal rats. These undifferentiated cells and also presumably immature epithelial cells in the progenitor zone of adult gastric glands were shown to express cholecystokinin-2 (CCK2) receptors and are therefore targets for the trophic action of gastrin.

H,K-ATPase-positive parietal cells in the progenitor zone of adult glands were also found to express CCK2 receptors, indicating that gastrin may stimulate maturation of the parietal cell lineage even during adult life. Parietal cells located in the upper region of the glandular unit are probably responsible for most of the acid secretion, because these cells were found to express the membrane-cytoskeletallinker ezrin, reported to be present in the canaliculi of stimulated parietal cells.

Pulse-labelling with 5-bromo-2'-deoxyuridine showed that during the gestational period, when the main motphological conformations and maturation of the gastric epithelium occur, proliferating cells appear at the basal epithelial cell layer and migrate towards the gastric lumen. This indicates that epithelial-mesenchymal cell and cell-matrix interactions may be involved in regulation of the cell proliferation and differentiation. Investigation of the expression of extracellular matrix proteins in foetal rat stomachs revealed a marked increase in collagen type I, suggesting that collagen, which is known to stimulate epithelial cell proliferation, is involved in the initial folding of the embryonic epithelium and formation of glandular structures.

In experiments in vitro, development of mucus-producing cells from undifferentiated gastric epithelial cells was stimulated by collagens but inhibited by fibronectin and laminin. In adult gastric epithelium, collagen type I was present only in the pit region of the glandular unit, where surface mucous cells are located. Thus, collagen type I, which is overexpressed in gastric ulcers and gastric cancers, likely stimulates proliferation of mucus-producing cells.

In conclusion, expression of CCK2 receptors was detected in foetal gastric epithelium and in the progenitor zone of adult gastric epithelium, implying that gastrin exerts trophic effects on immature gastric epithelial cells, during both stomach organogenesis and adult life. The spatial and temporal expression of extracellular matrix proteins and the effects of these proteins on development of mucus-producing cells in vitro indicate that extracellular matrix proteins may play an important role in regulation of epithelial cell proliferation and differentiation, and thus in the maintenance of normal cellular composition and function ofthe gastric epithelium.

Place, publisher, year, edition, pages
Linköping: Linköpings universitet, 2000. 82 p.
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 638
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-25719 (URN)10096 (Local ID)91-7219-739-0 (ISBN)10096 (Archive number)10096 (OAI)
Public defence
2000-09-22, Berzeliussalen, Universitetssjukhuset, Linköping, 13:00 (Swedish)
Opponent
Available from: 2009-10-08 Created: 2009-10-08 Last updated: 2012-11-09Bibliographically approved

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