Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038358 (gastric ulcer)
 5,179 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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 up-regulation 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.
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PMID:Novel roles of local insulin-like growth factor-1 activation in gastric ulcer healing: promotes actin polymerization, cell proliferation, re-epithelialization, and induces cyclooxygenase-2 in a phosphatidylinositol 3-kinase-dependent manner. 1739 62

Basic fibroblast growth factor (bFGF) is essential for gastric ulcer healing, whereas glucocorticoids delay gastric ulcer healing. We found that dexamethasone inhibited bFGF-stimulated rat gastric epithelial RGM-1 cells proliferation and attempted to elucidate the possible mechanistic pathway. Flowcytometry was used to determine cell proliferation. Western blot and RT-PCR were performed to evaluate changes in signaling pathways. Results showed that bFGF significantly increased mRNA expression of FGF receptor (FGFR)1 and FGFR2 at 10 min and increased expression of phosphorylated extracellular signal-regulated kinase (pERK1/pERK2) but not phosphorylated p38 mitogen-activated protein kinase (MAPK) or phosphorylated phosphatidylinositol 3-kinase (PI3K) within 30 min. This was followed by an increase of cyclooxygenase (COX)-2 mRNA and protein expression at 30 and 240 min, respectively. Mitogen-activated protein kinase kinase (MEK) inhibitor-PD98059 (10(-5) M) markedly suppressed bFGF-stimulated COX-2 expression and cell proliferation, but neither p38 MAPK inhibitor-SB203580 nor PI3K inhibitor-Wortmannin had any effect. Dexamethasone (10(-6)M) substantially reduced bFGF-stimulated ERK activation at 10 min, COX-2 mRNA and protein expression at 30 and 240 min, respectively, and prostaglandin E(2) synthesis at 8 h. Dexamethasone (10(-6) M) also significantly decreased mRNA expression of FGFR1 and FGFR2 at basal and bFGF-stimulated conditions at 10 min. This study indicated that bFGF-stimulated gastric epithelial RGM-1 cells proliferation via up-regulating FGFR1 and FGFR2, activating ERK1/ERK2 signal transduction pathway and COX-2 pathway. Dexamethasone significantly suppresses bFGF-stimulated RGM-1 cells proliferation in part via down-regulation of FGFR1/FGFR2, then decreasing bFGF-stimulated activation of ERK1/ERK2, followed by inhibition of COX-2 activation, and finally DNA synthesis.
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PMID:Dexamethasone inhibits basic fibroblast growth factor-stimulated gastric epithelial cell proliferation. 1869 28

Parkinson's disease (PD) is the second most common neurodegenerative disease, frequently associated with a gastric ulcer. We aimed to investigate the adropin neuroprotective/gastroprotective potential in the indomethacin (IND)-induced gastric ulcer in a rotenone-induced PD model. Rats were randomly divided into four groups: normal control group, rotenone/IND treated (PD /Ulcer) group, adropin treated PD/Ulcer group, and l-dopa/omeprazole (Om) treated PD/Ulcer group. There were ten rats selected for the normal control group. Striatal dopamine (DA), apoptosis/redox status, and motor/behavioral impairments were evaluated. Gastric oxidative stress, H+/K+-ATPase activity, prostaglandin E2, mucin content, and von Willebrand factor were measured. Gastric/striatal phosphatidylinositol 3-kinase (PI3K)/phosphorylated Akt and gastric vascular endothelial growth factor (VEGF)/striatal P53 immunoreactivities were checked. Striatal P53 upregulated modulator of apoptosis (Puma)/gastric vascular endothelial growth factor receptor-2 (Vegfr-2) expressions were evaluated. Adropin successfully restored striatal DA and attenuated rotenone-induced motor/behavior deficits along with strong gastroprotective potential, possibly through antioxidant activity via reduction in malondialdehyde level and upregulated superoxide dismutase, catalase activities, and serum ferric reducing antioxidant power. Adropin restored the delicate balance between the defective pro-survival PI3K/Akt/murine double minute 2 signals and apoptotic P53/Puma pathways. Adropin can be considered as a uniquely attractive therapeutic target in PD and its associated gastric ulcer.
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PMID:Unique Novel Role of Adropin in a Gastric Ulcer in a Rotenone-Induced Rat Model of Parkinson's Disease. 3283 26