Increased expression of epidermal growth factor receptor during gastric ulcer healing in rats

Tarnawski, Andrzej S.; Stachura, Jerzy; Durbin, Theodore; Sarfeh, I. James; Gergely, Hella

doi:10.1016/0016-5085(92)90123-g

Cited by 176 publications

(111 citation statements)

References 12 publications

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“…EGF produced by salivary glands and by the gastric mucosa plays a crucial role in the protection and repair of the gastrointestinal mucosa, and EGF receptors (EGFRs) are present on the epithelial cells lining the gut [Olsen et al, 1984;Thompson, 1988;Miller and Debas, 1995;Konturek et al, 1997]. Injury-induced increases in the production of EGF and over-expression of the EGFR have been observed during mucosal repair [Tarnawski et al, 1992]. EGF activates MEK1, and we have shown that expression of CA-MEK1 restores migration in polyamine-depleted cells [Vaidya et al, 2005].…”

Section: Discussionmentioning

confidence: 99%

MEK/ERK regulates adherens junctions and migration through Rac1

Ray

Vaidya

Johnson

2006

Cell Motil. Cytoskeleton

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Polyamine depletion with the ornithine decarboxylase inhibitor a-difluoromethyl ornithine (DFMO), prevents Rac1 activation causing the formation of a thick actin cortex at the cell periphery and inhibits migration of intestinal epithelial cells. In the present study, we demonstrate that MEK activation by EGF increased Rac1 activation, dissociation of intercellular contacts, and migration in both control and polyamine-depleted cells, while U0126, a specific inhibitor of MEK1, prevented disruption of junctions as well as EGF-induced Rac1 activation. Constitutively active MEK1 (CA-MEK) expression altered cell-cell contacts in control and polyamine depleted cells. The expression of constitutively active Rac1 (CA-Rac1) restored b-catenin to the cell periphery and prevented the formation of actin cortex and caused the appearance of F-actin stress fibers in polyamine-depleted cells. Inhibition of Rac activation by NSC23766, a specific inhibitor of Tiam1, an upstream guanidine nucleotide exchange factor for Rac1, reproduced the b-catenin localization and actin structure of polyamine-depleted cells. Tiam1 localized more extensively with b-catenin at the cell periphery in CA-Rac1 cells compared to vector cells. Polyamine depletion decreased the expression of E-cadherin to a greater extent compared to b-catenin. Subcellular fractionation further confirmed our immuno-localization and western blotting observations. These data suggest that EGF acting through MEK1/ERK to activate Rac1 regulates cell-cell contacts. Thus, decreased migration in polyamine depleted cells may be due to the inhibition of Tiam1 activation of Rac1 and the subsequent decreased expression of b-catenin and E-cadherin leading to reduced cell-cell contacts. Cell Motil.

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Section: Discussionmentioning

confidence: 99%

MEK/ERK regulates adherens junctions and migration through Rac1

Ray

Vaidya

Johnson

2006

Cell Motil. Cytoskeleton

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“…Gastric ulcers were induced in rats by a focal, serosal application of 100% acetic acid to the glandular portion of the stomach for 90 seconds by using a 4.0-mm inner diameter polyethylene tube as previously described. 18 A separate group of rats was subjected to sham operation without application of acetic acid. Rats were euthanized at 4, 6, and 12 days after ulcer induction, the stomach opened, and mucosal specimens of ulcerated or control mucosa obtained.…”

Section: Rat Gastric Ulcer Inductionmentioning

confidence: 99%

“…18 Specimens of control and ulcerated stomach were fixed in 10% formalin, routinely processed, paraffinembedded, and sectioned. Sections were dewaxed and processed routinely using DAKO Target retrieval solution (DAKO, Carpinteria, CA) for unmasking of antigen before blocking.…”

Section: Immunohistochemistrymentioning

confidence: 99%

Novel Roles of Local Insulin-Like Growth Factor-1 Activation in Gastric Ulcer Healing

Nguyen

Chai

et al. 2007

The American Journal of Pathology

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The precise role of insulin-like growth factor (IGF)-1 in gastric ulcer healing is unknown. In experimental rat gastric ulcers, we examined expression of IGF-1 mRNA and protein by reverse transcriptase-polymerase chain reaction or enzyme-linked immunosorbent assay and immunostaining, respectively. In cultured rat gastric epithelial RGM1 cells, we examined effects of exogenous IGF-1 on cell migration, re-epithelialization, and proliferation-essential components of ulcer healing. We also examined whether IGF-1 induces cyclooxygenase (COX)-2 expression and determined the role of phosphatidylinositol 3-kinase and mitogen-activated protein kinase signaling pathways in mediating IGF-1 actions. Gastric ulceration triggered an approximately threefold increase in IGF-1 expression in epithelial cells of the ulcer margins (P < 0.001 versus control), especially in cells re-epithelizing granulation tissue and in mucosa in proximity to the ulcer margin. Treatment of RGM1 cells with IGF-1 caused a dramatic increase in actin polymerization, an eightfold increase in cell migration (P < 0.001), a 195% increase in cell proliferation (P < 0.05), and a sixfold increase in COX-2 expression (P < 0.01). Inhibitor of phosphatidylinositol 3-kinase abolished IGF-1-induced RGM1 cell migration and proliferation, actin polymerization, and COX-2 expression. The upregulation of IGF-1 in gastric ulcer margin accelerates gastric ulcer healing by promoting cell re-epithelization, proliferation, and COX-2 expression via the phosphatidylinositol 3-kinase pathway. (Am J Pathol

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“…10 Increased healing has been associated with preserved contractility of the proper muscle layer, which is usually damaged in patients with peptic ulcers, 11 and the increased blood supply at the margin of EMR-in-duced ulcers resulting from increased levels of nitric oxide, epidermal growth factor and endogenous prostaglandins. 12,13 The healing process of ESD-induced ulcers may be similar to EMR-induced ulcers. A recent study comparing the healing rate of EMR-induced ulcers with regard to the duration of treatment with omeprazole suggested that one week of treatment may be sufficient.…”

Section: Discussionmentioning

confidence: 99%

A Matched Case-Control Study of a Novel Acid-Pump Antagonist and Proton-Pump Inhibitor for the Treatment of Iatrogenic Ulcers Caused by Endoscopic Submucosal Dissection

Kim

Jang

Kim³

2010

Gut Liver

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Background/Aims: Revaprazan, a novel acid-pump antagonist, and proton-pump inhibitors (PPIs) have pH-independent effects on ulcer healing. The addition of a PPI promotes the cell restitution rate as well as vessel regeneration and maturation for ulcer repair. Revaprazan is known to protect the mucosa by increasing the prostaglandin concentration. Methods: We reviewed the medical records of patients who underwent endoscopic submucosal dissection (ESD) for gastric neoplasia at Yeungnam University Hospital between January 2008 and May 2009. We conducted a matched case-control study to compare the healing rates effected by revaprazan and rabeprazole. Results: Each group consisted of 30 patients. The baseline characteristics did not differ significantly between the two groups. Stage S1 disease was observed in 97% and 100% of patients after 8 weeks of treatment in the revaprazan and rabeprazole groups, respectively. In the revaprazan group, only one patient had stage H2 disease: a 54-year-old man with a 5.5-cm lesion after ESD of the ulcer, type IIa early gastric cancer, and adenocarcinoma. No serious adverse effects occurred during the treatment period in either group. Conclusions: The safety and efficacy profiles of revaprazan and rabeprazole are similar for the treatment of ESD-induced ulcers. (Gut Liver 2010; 4:25-30)

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Increased expression of epidermal growth factor receptor during gastric ulcer healing in rats

Cited by 176 publications

References 12 publications

MEK/ERK regulates adherens junctions and migration through Rac1

MEK/ERK regulates adherens junctions and migration through Rac1

Novel Roles of Local Insulin-Like Growth Factor-1 Activation in Gastric Ulcer Healing

A Matched Case-Control Study of a Novel Acid-Pump Antagonist and Proton-Pump Inhibitor for the Treatment of Iatrogenic Ulcers Caused by Endoscopic Submucosal Dissection

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