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)

Clopidogrel is not safe enough for the gastric mucosa in patients with high risk of peptic ulcer. This study aimed to explore if clopidogrel delays gastric ulcer healing and elucidate the involved mechanisms. Gastric ulcer was induced in rats and the ulcer size, mucosal epithelial cell proliferation of the ulcer margin, expression of growth factors [epidermal growth factor (EGF), basic fibroblast growth factor] and their receptors, and signal transduction pathways for cell proliferation were measured and compared between the clopidogrel-treated group and untreated controls. For the in vitro part, rat gastric mucosal epithelial cell line (RGM-1 cells) was used to establish EGF receptor over-expressed cells. Cell proliferation and molecular change under EGF treatment (10ng/ml) with and without clopidogrel (10(-6)M) were demonstrated. Ulcer size was significantly larger in the clopidogrel-treated group compared to the control and mucosal epithelial cell proliferation of the ulcer margin was significantly decreased in the clopidogrel-treated group (P<0.05). Clopidogrel (2mg and 10mg/kg/day) significantly decreased ulcer-induced gastric epithelial cell proliferation and ulcer-stimulated expressions of EGF receptor and phosphorylated extracellular signal-regulated kinase (PERK) at the ulcer margin (P<0.05). Clopidogrel (10(-6)M) also inhibited EGF-stimulated EGF receptor, PERK expression, and cell proliferation in RGM-1 cells (P<0.05), and caused much less inhibition of EGF-stimulated cell proliferation in EGF receptor over-expressed RGM-1 cells than in RGM-1 cells (22% vs. 32% reduction). In conclusion, clopidogrel delays gastric ulcer healing in rats via inhibiting gastric epithelial cell proliferation, at least by inhibition of the EGF receptor-ERK signal transduction pathway.
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PMID:Clopidogrel delays gastric ulcer healing in rats. 2297 10

Bleeding and delayed healing of gastric ulcer are well-recognized in patients following Clopidorgrel treatment. Our previous studies have shown that endoplasmic reticulum stress (ER) is involved in Clopidogrel-induced gastric mucosal damage through activating p38 mitogen-activated protein kinases (MAPK) pathway. This present study aims to further investigate the role of MAP kinase phosphatase 5 (MKP-5), a MKP known to dephosphorylate and inactivate p38/MAPK, in Clopidogrel-induced gastric mucosal injury and the underlying mechanisms. It shows that MKP-5 is down-regulated at both mRNA and protein levels in the gastric mucosa from bleeding patients who took Clopidogrel over one year. In vitro study using human gastric epithelial cell line GES-1 demonstrates that exposure to Clopidorgrel (1.0-2.0 mM) increases phosphorylation of p38/MAPK and decreases MKP-5 expression simultaneously. Overexpression of MKP-5 promotes GES-1 cell proliferation and reduces apoptosis following Clopidogrel exposure. Interestingly, overexpression of MKP-5 also attenuates Clopidorgrel-induced tight junction (TJ) destruction by down-regulating expression of ER stress-related protein C/EBP homologous protein (CHOP) and tribbles pseudokinase 3 (TRIB3). These three effects, increased proliferation, reduced apoptosis and attenuated TJ destruction, are regulated through inhibited phosphorylation of p38/MAPK signaling pathway. We conclude that MKP-5 is down-regulated in Clopidogrel-induced gastric mucosa injury in vivo and in vitro via phosphorylation and activation of p38/MAPK signaling pathway. Overexpression of MKP-5 reverses Clopidogrel-induced gastric mucosal injury. These findings imply that MKP-5 may be a potential therapeutic target in Clopidogrel-induced gastric mucosal injury and bleeding.
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PMID:Role of MKP-5-p38/MAPK pathway in Clopidogrel-induced gastric mucosal epithelial cells apoptosis and tight junction dysfunction. 3250 73