Analysis of gastrin receptor gene expression in proliferating cells in the neck zone of gastric fundic glands using laser capture microdissection

Kazumori, Hideaki; Ishihara, Shunji; Kawashima, Kousaku; Fukuda, Ryo; Chiba, Tsutomu; Kinoshita, Yoshikazu

doi:10.1016/s0014-5793(01)02084-1

Cited by 34 publications

(21 citation statements)

References 55 publications

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“…Fresh frozen colon tissues were cut into 5-m-thick sections using a cryostat, then mounted on noncoated glass slides, fixed immediately with 70% ethanol for 30 s, and washed with diethylpyrocarbonate (DEPC)-treated water for 30 s. Next, the sections were stained rapidly with hematoxylin for 30 s, dehydrated by passage through an ethanol gradient, counterstained with eosin Y for 1 min, dehydrated again with an ethanol gradient, cleared with xylene, and air-dried. The sections were laser microdissected using the laser-capture microdissection (LCM) system LM200 (Olympus, Tokyo, Japan), as reported previously (18). In brief, tissue sections on slides were placed on the stage of a microscope, and an area of tissue was selected and covered with LCM transfer film.…”

Section: Methodsmentioning

confidence: 99%

“…Samples captured by 5,000 shots on each transfer film cap were immersed in RNA extraction solution. To exclude the possibility that contaminating cells within the colonic epithelial preparation may be responsible for the detection of RPTP-␤ expression, we performed RT-PCR to detect the cytokeratin-20 (an epithelial maker) and CD45 (pan-leukocyte maker) mRNA simultaneously in LCM samples, as reported previously (13,18,36).…”

Section: Methodsmentioning

confidence: 99%

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Increased expression of midkine in the rat colon during healing of experimental colitis

Yuki

Ishihara²,

Rumi³

et al. 2006

American Journal of Physiology-Gastrointestinal and Liver Physi

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Midkine (MK) is a unique growth and differentiation factor that modulates the proliferation and migration of various cells; however, little is known regarding its relationship to intestinal diseases. The aim of this study was to investigate MK expression and its role in dextran sulfate sodium (DSS)-induced colitis in rats. The expressions of MK, receptor-like protein-tyrosine phosphatase (RPTP)-β, and proinflammatory cytokines were examined in rat colonic tissues after the development of DSS-induced colitis using Northern blotting, immunohistochemistry, and laser-capture microdissection (LCM) coupled with RT-PCR. The effects of MK on the migration of intestinal epithelial cells (IEC-6) were also evaluated in vitro using an intestinal wound repair model. MK expression was significantly increased in damaged colonic mucosa, mainly from day 3 to day 5 after the end of DSS administration, with abundant MK immunoreactive signals detected in submucosal fibroblasts. Expressions of proinflammatory cytokines were most strongly induced on day 1, which preceded the augmentation of MK expression. Results of LCM coupled with RT-PCR clearly indicated RPTP-β expression in colonic epithelial cells. The migration assay showed that wound repair in the MK-treated groups was accelerated dose dependently. The present results showed for the first time that intestinal inflammation upregulates the MK-RPTP-β system, which may stimulate mucosal regeneration during the process of healing of colitis. Additional investigations regarding the role of MK may contribute to the development of new options for the treatment of inflammatory bowel diseases.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Increased expression of midkine in the rat colon during healing of experimental colitis

Yuki

Ishihara²,

Rumi³

et al. 2006

American Journal of Physiology-Gastrointestinal and Liver Physi

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“…Moreover, Hirayama et al (1999) have shown that poorly differentiated adenocarcinomas as well as carcinoid tumors develop during H. pylori-induced gastritis with hypergastrinemia. Recent studies have shown that gastrin receptors are present on gastric mucosal progenitor cells, suggesting that gastrin has direct trophic actions on gastric mucosal cells (Kazumori et al, 2001;Nakajima et al, 2002). On the other hand, several investigators have reported that gastrin promotes gastric mucosal cell proliferation indirectly by stimulating the production of growth factors such as TGF-␣, heparinbinding epidermal growth factor-like growth factor, and Reg (Fukui et al, 1998;Miyazaki et al, 1999;Wang et al, 2000).…”

Section: Fukui Et Almentioning

confidence: 99%

Effects of Helicobacter pylori Infection on the Link between Regenerating Gene Expression and Serum Gastrin Levels in Mongolian Gerbils

Fukui

Franceschi

Penland

et al. 2003

Laboratory Investigation

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SUMMARY:Although regenerating gene (Reg) protein is reported to have a trophic effect on gastric epithelial cells, its involvement in human gastric diseases is not clear. We have recently shown that both gastrin and gastric mucosal inflammation enhance Reg gene expression in the fundic mucosa in rats. This study was designed to clarify whether Reg protein is involved in Helicobacter pylori-induced gastritis and whether Reg gene expression is linked to serum gastrin levels in this condition. Mongolian gerbils were inoculated with an H. pylori strain isolated from a gastric cancer patient. Four weeks later, some of the gerbils with H. pylori infection were eradicated by lansoprazole, amoxicillin, and clarithromycin. The time courses of changes in Reg gene expression, serum gastrin levels, gastric acidity, and histopathologic factors were examined. Four weeks after H. pylori infection, gastritis started spreading to the fundic mucosa, and gastric acidity started reducing. Serum gastrin levels and Reg mRNA expression in the fundus were significantly increased 6 weeks after infection. Reg mRNA expression in the fundus correlated significantly with both serum gastrin levels and the severity of fundic mucosal inflammation. After H. pylori eradication, serum gastrin levels and fundic mucosal inflammation were normalized, and the increase in Reg mRNA expression was abolished. The Reg gene is associated with hypergastrinemia and fundic mucosal inflammation and may be involved in H. pylori-induced gastritis. (Lab Invest 2003, 83:1777-1786.

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“…Rat toxicity studies conducted during the development of the world's first clinical application of PPI also reDepartment of Internal Medicine, Saga Medical School, Japan and Departments of Comprehensive Medicine and Psychosomatic Medicine, Tohoku University Hospital, Japan vealed that enterochromaffin-like (ECL) cell carcinoids develop in the stomach as a result of long-term PPI administration (6). Long-standing hypergastremia resulting from the potent gastric acid-suppressing action of PPI is believed to be a major factor in this, because gastrin might have a trophic effect on gastric mucosal cells (7). Considering those concerns, many clinical studies involving the long-term administration of PPI for several years have been conducted in Europe and the US, confirming the absence of problems in terms of tolerability (8)(9)(10)(11).…”

Section: Introductionmentioning

confidence: 99%

Safety and Efficacy of Long-Term Maintenance Therapy with Oral Dose of Rabeprazole 10 mg Once Daily in Japanese Patients with Reflux Esophagitis

Fujimoto

Hongo

Group³

2011

Intern. Med.

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Objective The aim of this prospective clinical study was to evaluate the efficacy and safety of long-term proton pump inhibitor (PPI) treatment for two years in Japanese patients with reflux esophagitis (RE). Methods The efficacy and safety of two-year (104-week) treatment with rabeprazole (RPZ) 10 mg were studied in patients confirmed to have been cured of RE by PPI and who required long-term maintenance therapy with PPI. We performed serial endoscopy, checked gastroesophageal reflux disease (GERD) symptoms, adverse events, laboratory values and serum gastrin. We also monitored gastric mucosal histology, atrophy and polyps. Results The endoscopic non-relapse rate for RE was 87.3% for the 104-week period. GERD symptoms improved based on the fact that the mean change from baseline in GERD symptom score after treatment was a negative value. Treatment was safe; and atrophy was found to have developed in virtually no cases. A few new benign fundic gland or hyperplastic polyps developed throughout the study, but no ECL carcinoids were found to have developed. Serum gastrin levels tended to increase up to 24 weeks, but there were no subsequent changes thereafter up to 104 weeks. Conclusion The results confirmed oral RPZ 10 mg to be effective for maintenance therapy in Japanese patients with RE. Although effects on the gastric mucosa were not ruled out, long-term use of RPZ was confirmed to be safe overall.

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Analysis of gastrin receptor gene expression in proliferating cells in the neck zone of gastric fundic glands using laser capture microdissection

Cited by 34 publications

References 55 publications

Increased expression of midkine in the rat colon during healing of experimental colitis

Increased expression of midkine in the rat colon during healing of experimental colitis

Effects of Helicobacter pylori Infection on the Link between Regenerating Gene Expression and Serum Gastrin Levels in Mongolian Gerbils

Safety and Efficacy of Long-Term Maintenance Therapy with Oral Dose of Rabeprazole 10 mg Once Daily in Japanese Patients with Reflux Esophagitis

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