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)

Once a peptic ulcer has developed, angiogenesis plays a critical role in its healing by enhancing the microcirculation in the healing site. Previous reports have shown that Helicobacter pylori infection delays the healing of chronic gastric ulcers. To elucidate the mechanism of delayed ulcer healing caused by H. pylori, we investigated the angiogenic phenotype and expression of receptors of angiogenic growth factors in vascular endothelial cells. After human umbilical vein endothelial cells (HUVECs) were treated with H. pylori water extract, angiogenic phenotype was determined by capillary tube formation and DNA synthesis assay. The expressions of the receptors of vascular endothelial growth factor and angiopoietin-1/-2 were assessed by reverse transcription-polymerase chain reaction and Western blot analysis in HUVECs and by double immunofluorescent staining in gastric mucosa. Angiogenic signaling in HUVECs was evaluated by using a quantitative intracellular calcium mobilization assay. H. pylori water extract significantly inhibited capillary tube formation and DNA synthesis and down-regulated the expressions of receptors of vascular endothelial growth factor and angiopoietin in HUVECs. H. pylori water extract suppressed vascular endothelial growth factor-induced intracellular calcium signaling in HUVECs. H. pylori may inhibit the expression of angiogenic growth factor receptors in vascular endothelial cells, which could explain, in part, the delayed healing of gastric ulcer by H. pylori.
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PMID:Helicobacter pylori down-regulates the receptors of vascular endothelial growth factor and angiopoietin in vascular endothelial cells: implications in the impairment of gastric ulcer healing. 1525 99

The maintenance of gastric mucosal function and integrity highly depends on the status of microcirculation. Vasoactive agents--prostaglandins, nitric oxide and sensory neuropeptides (e.g. calcitonin gene-related peptide)--play a crucial role in mucosal defensive processes. Beside the local release of vasoactive mediators the central nervous system is also involved in regulation of gastric functions. Cerebral lesions, stimulation of different brain areas can result in gastric mucosal injury. Noxious challenge of gastric mucosa alters the sodium currents in gastric sensory neurons and induces cfos mRNA expression in nucleus tractus solitarii and area postrema. Vagal nerve has long been established to play a permissive role in the development of gastric lesions. However, several lines of evidences suggest its physiological relevance in the enhancement of gastric mucosal resistance. It was concluded that gastroprotection can be induced by low level of central vagal stimulation and the consequent release of prostaglandins, nitric oxide, and calcitonin gene-related peptide. Prostaglandins, nitric oxide and sensory neuropeptides play a role also in ulcer healing by stimulating the formation of growth factors, the epithelial proliferation and angiogenesis. Both systemic and local administration of growth factors accelerated the ulcer healing. Local, single injection of plasmid-DNA encoding vascular endothelial growth factor (VEGF) was shown to stimulate the ulcer healing in the rat. The transient, local expression of VEGF in ulcerated tissue might be a new therapeutic strategy in the treatment of gastric ulcer disease.
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PMID:Gastric mucosal protection: from prostaglandins to gene-therapy. 1563 36

We studied the relation of hypoxia-inducible factor-1alpha (HIF-1alpha) to vascular endothelial growth factor and vasoactive factors during the healing of gastric ulcers. The gastric ulcers were divided into three stages (active stage, healing stage and scar stage). The expression of HIF-1alpha, endothelin-1, inducible nitric oxide synthase, and vascular endothelial growth factor mRNA was highest during the active stage of ulcer healing, and endothelin-1, vascular endothelial growth factor protein levels and nitric oxide were higher during the healing stage. Thus, levels of HIF-1alpha mRNA tend to increase during the active stage of gastric ulcer healing, suggesting that this factor participates in the induction of endothelin-1, inducible nitric oxide synthase, and vascular endothelial growth factor. Also, the HIF-1alpha mRNA level did not differ significantly among the various stages of ulcer healing, and detectable levels of HIF-1alpha protein were not found during any stage. This suggests that these angiogenic factors and vasoactive substances may be induced by HIF-1alpha. During the active stage on endoscopic examination, considered the initial phase of ulcer healing, the process of ulcer healing has begun, and the tissue at the ulcer margin has already been reoxygenated.
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PMID:Relation of hypoxia-inducible factor-1alpha to vascular endothelial growth factor and vasoactive factors during healing of gastric ulcers. 1583 34

COX-1 and COX-2 are two cyclooxygenase enzymes responsible for prostanoid production. COX-2 is expressed in inflammatory cells and fibroblasts of the gastric mucosa, and through the production of various growth factors including hepatocyte growth factor (HGF) and vascular endothelial growth factor (VEGF), plays a key role in the tissue repair process. Aspirin induces and acetylates COX-2 to produce 15-(R)-epi-lipoxinA4, an anti-inflammatory mediator thought to protect the gastric mucosa against aspirin-induced injury. Recently, three different PGE synthases have been identified, that convert COX-2 metabolites into PGE2. mPGE synthase (mPGES)-1 has been shown to be inducible, and to colocalize with COX-2 in fibroblasts and macrophages infiltrating the gastric ulcer bed. cPGES and mPGES-2 have been found expressed in normal gastric mucosa, with no change in expression levels seen in gastritis or gastric ulcer tissue. Finally, this review discusses the role of these enzymes in the pathophysiology of the gastric mucosa, as well as the biologcal significance of their inhibition.
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PMID:The role of cyclooxygenase in gastric mucosal protection. 1618 16

1. Platelets contain an array of growth factors that can modulate healing processes, including both pro- (e.g., vascular endothelial growth factor (VEGF)) and antiangiogenic (e.g., endostatin) factors. Previous studies have shown that circulating platelets contribute significantly to gastric ulcer healing, acting as a delivery system for these growth factors to the site of injury. In this study, we examined the effects of orally administered human platelets on the healing of gastric ulcers in rats, and determined the contribution of VEGF and endostatin to healing in this model. 2. Twice-daily administration of human platelets significantly accelerated ulcer healing, but platelet-poor plasma (PPP), lysed platelets and serum failed to produce this effect. There was no correlation between ulcer healing and the levels of VEGF or endostatin in serum, PPP or platelet-rich plasma (PRP). 3. Accelerated ulcer healing could not be produced by oral administration of the angiogenic factors themselves, at concentrations matching those in PRP. 4. The accelerated healing induced by platelets could be reversed by immuno-neutralization of VEGF. In contrast, immuno-neutralization of endostatin did not affect PRP-induced ulcer healing. 5. These studies indicate that VEGF released from platelets accounts for the accelerated healing of gastric ulcers. However, as intact (rather than lysed) platelets were required for the accelerated healing, the presentation of VEGF by the platelet at the site of injury appears to be crucial for enhancement of the healing process.
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PMID:Platelets accelerate gastric ulcer healing through presentation of vascular endothelial growth factor. 1656 32

Probiotics are widely used as functional foods which have been advocated for the maintenance of gastrointestinal microflora equilibrium and treatment of gastrointestinal disorders. However, studying the role of probiotics in peptic ulcer disease is limited. The aim of the present study is to investigate the effect of a probiotic strain Lactobacillus rhamnosus GG on gastric ulcer and to elucidate the mechanisms involved. Gastric kissing ulcers were induced in rats by acetic acid (60% v/v). L. rhamnosus GG was given intragastrically at 10(8) cfu/day or 10(9) cfu/day for three consecutive days after ulcer induction. L. rhamnosus GG successfully colonized in the gastric mucosa especially at the ulcer margin. It also significantly and dose-dependently reduced gastric ulcer area. Cell apoptosis to cell proliferation ratio was strongly decreased and accompanied by significant up-regulation of ornithine decarboxylase (ODC) and B-cell lymphoma 2 (Bcl-2) protein expression at the ulcer margin. Angiogenesis was also significantly stimulated together with the induction of vascular endothelial growth factor (VEGF) expression. Furthermore, L. rhamnosus GG up-regulated the phosphorylation level of epidermal growth factor receptor (EGF receptor) without altering the total EGF receptor expression. These findings suggested that L. rhamnosus GG enhanced gastric ulcer healing via the attenuation of cell apoptosis to cell proliferation ratio and increase in angiogenesis. Regulators of these processes such as ODC, Bcl-2, VEGF and EGF receptor are likely to be involved in the healing action of L. rhamnosus GG for gastric ulcer.
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PMID:Probiotic Lactobacillus rhamnosus GG enhances gastric ulcer healing in rats. 1739 75

Mesenchymal stem cells (MSCs), a subpopulation of adult somatic stem cells, are an attractive stem cell source in regenerative medicine because of their multipotentiality. We examined the effects of MSC transplantation on gastric ulcer healing. Putative MSCs, isolated from bone marrow aspirates of male rats by dish adherence and expanded in culture, were characterized by flow cytometry and reverse transcription-polymerase chain reaction. Gastric ulcers were induced by serosal application of acetic acid on the anterior wall of the stomach in female rats. Either MSCs (labeled with PKH67; 1x10(7) cells) or vehicle was injected into the gastric wall surrounding the ulcer. The healing process of the ulcer and the influence of anti-vascular endothelial growth factor (VEGF) antibody were examined. CD29-positive, CD90-positive, CD34-negative, and CD45-negative MSCs expressed mRNAs for VEGF and hepatocyte growth factor (HGF). The MSCs were transplantable to the gastric tissue surrounding the ulcer, where a majority of the engrafted cells were positive for vimentin. The transplantation significantly accelerated gastric ulcer healing compared with controls. The engrafted MSCs also expressed VEGF and HGF. Administration of anti-VEGF neutralizing antibody dose dependently reduced the MSC-induced promotion of ulcer healing. In conclusion, MSC transplantation accelerated gastric ulcer healing, possibly through the induction of angiogenesis in the gastric mucosa via the secretion of VEGF. The beneficial effects of MSCs might be mediated not only by their differentiation into gastric interstitial cells, but also by their ability to supply angiogenic factors.
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PMID:Topical transplantation of mesenchymal stem cells accelerates gastric ulcer healing in rats. 1820 10

Gene therapy for gastric cancer and gastric ulcer is a rationalized strategy since various genes correlate with these diseases. Since gene expressions in non-target tissues/cells cause side effects, a selective gene delivery system targeted to the stomach and/or cancer must be developed. The route of vector transfer (direct injection, systemic, intraperitoneal, gastric serosal surface and oral administration) is an important issue which can determine efficacy and safety. Strategies for cancer gene therapy can be categorized as suicide gene therapy, growth inhibition and apoptosis induction, immunotherapy, anti-angiogenesis, and others. Combination of the target gene with other genes and/or strategies such as chemotherapy and virotherapy is promising. Candidates for treatment of gastric ulcer are vascular endothelial growth factor, angiopoietin-1, serum response factor, and cationic host defense peptide cathelicidin. In this review, we discuss stomach- and cancer-targeted gene transfer methods and summarize gene therapy trials for gastric cancer and gastric ulcer.
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PMID:Gene therapy for gastric diseases. 1853 93

Angiogenesis is crucial to all types of wound healing, including gastric ulcer healing. The most potent promoter of angiogenesis is vascular endothelial growth factor (VEGF). We hypothesized that a 15-amino acid peptide designed to mimic the angiogenic action of VEGF would accelerate gastric ulcer healing. Gastric ulcers were induced in mice by serosal application of acetic acid. Treatment with the VEGF mimetic accelerated gastric ulcer healing when administered orally or intraperitoneally, at a dose of 50 ng/kg or greater. Such healing was not observed when the reverse sequence pentadecapeptide or the full-length VEGF protein was administered. Contrary to our hypothesis, the VEGF mimetic did not significantly increase angiogenesis in the ulcerated stomach. The enhancement of ulcer healing by the VEGF mimetic occurred independently of cyclooxygenase-2 (COX-2) activity but was blocked by inhibitors of inducible nitric oxide synthase (iNOS). These results demonstrate that a VEGF mimetic is a potent stimulus for gastric ulcer healing, even when given orally. The effects of the mimetic were independent of stimulatory effects on angiogenesis and COX-2 activity but were dependent on iNOS-derived NO production.
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PMID:A vascular endothelial growth factor mimetic accelerates gastric ulcer healing in an iNOS-dependent manner. 1858 58

Tissue remodeling follows the initial phase of wound healing and stops inflammatory and scar-forming processes, then restores the normal tissue morphology. The human peptide Gly-(L-His)-(L-Lys) or GHK, has a copper 2+ (Cu(2+)) affinity similar to the copper transport site on albumin and forms GHK-Cu, a complex with Cu(2+). These two molecules activate a plethora of remodeling related processes: (1) chemoattraction of repair cells such as macrophages, mast cells, capillary cells; (2) anti-inflammatory actions (suppression of free radicals, thromboxane formation, release of oxidizing iron, transforming growth factor beta-1, tumor necrosis factor alpha and protein glycation while increasing superoxide dismutase, vessel vasodilation, blocking ultraviolet damage to skin keratinocytes and improving fibroblast recovery after X-ray treatments); (3) increases protein synthesis of collagen, elastin, metalloproteinases, anti-proteases, vascular endothelial growth factor, fibroblast growth factor 2, nerve growth factor, neutrotropins 3 and 4, and erythropoietin; (4) increases the proliferation of fibroblasts and keratinocytes; nerve outgrowth, angiogenesis, and hair follicle size. GHK-Cu stimulates wound healing in numerous models and in humans. Controlled studies on aged skin demonstrated that it tightens skin, improves elasticity and firmness, reduces fine lines, wrinkles, photodamage and hyperpigmentation. GHK-Cu also improves hair transplant success, protects hepatic tissue from tetrachloromethane poisoning, blocks stomach ulcer development, and heals intestinal ulcers and bone tissue. These results are beginning to define the complex biochemical processes that regulate tissue remodeling.
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PMID:The human tri-peptide GHK and tissue remodeling. 1864 25


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