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- Friis-Hansen, Lennart, et al.
(författare)
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Characteristics of gastrin controlled ECL cell specific gene expression
- 2007
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Ingår i: Regulatory Peptides. - : Elsevier BV. - 1873-1686 .- 0167-0115. ; 140:3, s. 153-161
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Tidskriftsartikel (refereegranskat)abstract
- Background: The ECL cells are histamine-producing endocrine cells in the oxymic mucosa that synthesize and secrete proteins and peptides. They are the primary target for gastrin and mediate the control of gastrin on acid secretion and oxyntic mucosal growth. Knowledge of the molecular biology of the ECL cell is therefore important for understanding gastric physiology. Accordingly, we wanted to identify genes that are characteristically expressed in the ECL cells and controlled by gastrin. Methods: Using Affymetrix GeneChips((R)), RNA expression profiles were generated from ECL cells isolated by counterflow elutriation from hyper- or hypogastrinemic rats. Contamination from non-endocrine cells was eliminated by subtraction of the expression profiles of the fundic and antral mucosa. Results: The expression of 365 genes was ECL cell characteristic. Gastrin was found to control the expression of 120 which could be divided into two major groups depending on the known or anticipated biological function of the encoded protein: genes encoding proteins involved in the secretory process and genes encoding proteins needed to generate energy for secretion. Interestingly, gastrin stimulation also increased ECL cells expression of anti-apoptotic genes. Conclusion: The ECL cell specific expression profile is reminiscent of that of neurons and other endocrine cells exhibiting high expression of genes encoding proteins involved in the synthesis, storage and secretion of neuropeptides or peptide hormones. Gastrin regulated the expression of one third of these genes and is thus involved in the control of secretion from the ECL cells.
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- Friis-Hansen, Lennart, et al.
(författare)
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Gastric inflammation, metaplasia, and tumor development in gastrin-deficient mice
- 2006
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Ingår i: Gastroenterology. - : Elsevier BV. - 1528-0012 .- 0016-5085. ; 131:1, s. 246-258
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Tidskriftsartikel (refereegranskat)abstract
- Background & Aims: Gastrin deficiency and proton pump inhibitor treatment cause achlorhydria, which predisposes to disease. To elucidate the underlying molecular biology, we examined the changes in gastric gene expression in both types of achlorhydria. We also explored the associated changes in the gastric microflora and the long-term consequences of gastrin-deficient achlorhydria. Methods: Expression profiles were generated from gastric RNA from wild-type mice, gastrin knockout (KO) mice, gastrin KO mice after I week of gastrin infusion, and wild-type mice treated for I month with a proton pump inhibitor. The results were confirmed using real-time polymerase chain reaction and immuno-histochemistry. Selective media were used to characterize the gastric microflora. Results: The number of gastric bacteria was increased in both gastrin KO and PPI-treated mice. The expression profiles revealed activation of immune defense genes, interferon-regulated response genes, and intestinal metaplasia of the gastric mucosa. In young gastrin-deficient mice, gastrin infusions reversed the changes. Over time, the changes accumulated, became irreversible, and progressed into metaplasia and polyp development. Finally, the study showed that gastrin regulated the expression of genes encoding extracellular matrix proteins. Conclusions: Independently of gastrin, achlorhydria is associated with gastric bacterial overgrowth and intestinal gene expression patterns and is associated with predisposition to disease. Gastrin is therefore essential for prevention of gastric disease, mainly through control of acid secretion but to a lesser extent also through control of gastric gene expression. The gastrin-deficient mouse serves as a useful new model for gastric metaplasia and neoplasia.
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- Friis-Hansen, Lennart, et al.
(författare)
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Reduced ghrelin, IAPP and PYY expression in the stomach of gastrin-cholecystokinin knockout mice.
- 2005
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Ingår i: Endocrinology. - : The Endocrine Society. - 0013-7227 .- 1945-7170. ; 146:10, s. 4464-4471
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Tidskriftsartikel (refereegranskat)abstract
- The antral hormone gastrin and its intestinal relative, cholecystokinin (CCK), are pivotal in the regulation of gastric functions. Other gastric hormones like ghrelin, peptide YY (PYY), and islet amyloid polypeptide (IAPP), however, also contribute to the regulation of acid secretion, motility, and feeding. Because gastrin and CCK are crucial for gastric homeostasis, we examined how loss of gastrin alone and gastrin plus CCK affected the expression of ghrelin, IAPP, and PYY and ghrelin secretion. The expression of ghrelin, IAPP, and PYY and the CCK-A receptor genes were examined in both gastrin and gastrin-CCK double-knockout (KO) mice using immunocytochemistry and quantitative RT-PCR. Ghrelin concentrations in plasma were measured using RIA. Gastrin and CCK were infused in gastrin-CCK KO mice using osmotic minipumps. The number of ghrelin cells and ghrelin gene expression were unaffected, albeit the ghrelin cells were located closer to the base of the glands in both KO mouse strains when freely fed. However, lack of both gastrin and CCK attenuated fasting-induced ghrelin expression and secretion. Fundic ghrelin cells expressed the CCK-A receptor, and ghrelin expression increased after CCK infusion. Furthermore, gastric IAPP and PYY expression as well as the number of IAPP- and PYY-containing cells were reduced in both gastrin and gastrin-CCK KO mice. Gastrin infusion increased gastric IAPP but not PYY expression. In conclusion, lack of gastrin plus CCK but not gastrin alone reduced ghrelin secretion in response to fasting through both direct and indirect mechanisms. Both gastrin and combined gastrin-CCK deficiency reduced the gastric IAPP and PYY expression.
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- Friis, Lennart
(författare)
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Health of municipal sewage workers : Studies of cancer incidence, biomarkers of carcinogenicity and genotoxicity, and self reported symptoms
- 2001
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The occupational exposures of sewage workers are complex and variable, and include a great variety of biological and chemical agents. Previous research has focused mostly on infections and various symptoms among sewage workers, e.g. abdominal and respiratory symptoms. At several sewage plants in Sweden, concern arose about occupational cancer, specifically cancer of the stomach, the kidney, and the lung. The aim of this study was to study the cancer incidence among municipal sewage workers, some exposures that might be connected with cancer risk, and self reported abdominal and respiratory symptoms. In a cohort of municipal sewage workers there was no increase in the overall incidence of cancer when compared with the general population. However, there was a slight increase in the incidence of prostate cancer, but not in the sites of original concern among the workers. Infection by the gastric carcinogen Helicobacter pylori (determined from the presence of IgG antibodies in serum against H pylori) was no more prevalent in sewage workers than in comparable referents. Neither were sewage workers more exposed to genotoxic agents than comparable referents, as measured by the alkaline single cell gel electrophoresis (SCG) assay performed on peripheral lymphocytes. There was no increase in the three-month prevalence of abdominal symptoms when compared with other municipal workers. Specifically, there was no difference in prevalence of the common disorders dyspepsia and irritable bowel syndrome. Sewage workers reported adult bronchial asthma significantly more than the referents.
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