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Effects of Extracellular Matrix Proteins on Development of Fetal Rat Gastric Epithelial Cells in Culture
Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
Discovery, Research Area CV & GI, AstraZeneca R&D Mölndal, Mölndal, Sweden.
Discovery, Research Area CV & GI, AstraZeneca R&D Mölndal, Mölndal, Sweden.
Department of Physiological Sciences, Section for Neuroendocrine Cell Biology, Lund University, Lund, Sweden.
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(English)Manuscript (preprint) (Other academic)
Abstract [en]

Undifferentiated fetal gastric epithelial cells and stem cells of adult gastric glands give rise to surface mucous, parietal, mucous neck, zymogenic, caveolated, and endocrine cells by yet-unknown mechanisms. Our aim was to establish an in vitro model for investigating the effects of extracellular matrix proteins on development of gastric epithelial cells, and to determine whether collagen type I affects growth and maturation of undifferentiated epithelial cells. Fetal rat gastric cells were isolated and then cultured for 15 days on uncoated glass coverslips or on collagen types I or IV, fibronectin, or laminin. The appearance of epithelial cells was investigated by means of Alcian blue-periodic acid Schiff (AB-PAS) staining, inununostaining for cytokeratin, H,K-ATPase and chromogranin A, acridine orange accumulation, and by transmission and scamting electron microscopy. AB-PAS-positive cells containing mucous-type granules were detected. These mucoid cells were abundant on uncoated coverslips and collagen, but scarce on fibronectin and laminin. No cytokeratin, H,K-ATPase or chromogranin A, or increased acridine orange accumulation in response to secretagogues were observed. Rarely, endocrine cells were observed by electron microscopy. In conclusion, undifferentiated epithelial cells did proliferate and differentiate, and mucoid and endocrine cells matured in the established in vitro system. Moreover, development of mucoid cells from undifferentiated gastric epithelial cells was stimulated by collagen matrices but inhibited by fibronectin and laminin.

Keyword [en]
collagen, cell differentiation, electron microscopy, endocrine cells, epithelium, fibronectin, laminin, mucoid cells, stomach
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:liu:diva-79725OAI: oai:DiVA.org:liu-79725DiVA: diva2:544014
Note
Running title: Development of gastric epithelial cellsAvailable from: 2012-08-13 Created: 2012-08-13 Last updated: 2012-08-13Bibliographically 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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