UMLS:C0038358 - FACTA Search

Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Target Concepts:

Query: UMLS:C0038358 (gastric ulcer)
5,179 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Angiogenesis plays a pivotal role in gastric ulcer repair. Several growth factors are involved in angiogenesis, and of these, vascular endothelial growth factor (VEGF) has received considerable attention, since it is the only factor that specifically acts on endothelial cells. However, the role of VEGF in gastric ulcer repair is not known. In the present study, we demonstrate the specific expression of VEGF at the gastric ulcer margin, using immunohistochemistry and RT-PCR. The specific receptors of VEGF, flt-1 and KDR were also detected in gastric mucosa. We further demonstrate the expression of VEGF by cultured human gastric fibroblasts which is enhanced by tumor necrosis factor-alpha. These data suggest that VEGF may play a role in angiogenesis in the process of gastric ulcer healing.
...
PMID:Expression of vascular endothelial growth factor at the human gastric ulcer margin and in cultured gastric fibroblasts: a new angiogenic factor for gastric ulcer healing. 917

Angiogenesis plays an important role in gastric ulcer repair. Several growth factors are involved in angiogenesis and, of these, vascular endothelial growth factor (VEGF) has received considerable attention because it is the only factor that acts specifically on endothelial cells and, unlike other angiogenic growth factors, has the hydrophobic signal peptide required for extracellular transport according to classical secretory pathways. We have lately demonstrated the role of VEGF in gastric ulcer repair. Previous reports confirmed that sofalcone has remarkable effects on gastric ulcer healing, which may be mediated by its stimulatory effect on prostaglandin (PG) release in gastric cells. Our data indicate that PGs stimulate VEGF expression in gastric fibroblasts. In this report we hypothesize that the clinical effect of sofalcone is mediated by VEGF expression and we demonstrate that sofalcone stimulates VEGF release by gastric fibroblasts in primary culture.
...
PMID:The possible role of vascular endothelial growth factor (VEGF) in gastric ulcer healing: effect of sofalcone on VEGF release in vitro. 987 18

Cigarette smoking is associated with peptic ulcer diseases. Smokers have lower levels of salivary epidermal growth factor (EGF) than nonsmokers. We investigated whether reduction of EGF is involved in the delay of gastric ulcer healing by cigarette smoking. Rats with acetic acid-induced ulcers were exposed to cigarette smoke (0, 2, or 4% vol/vol) 1 day after ulcer induction. EGF level was elevated 1 day after ulcer induction in salivary glands and serum, and 4 days after ulcer induction in the gastric mucosa. However, cigarette smoke depressed these beneficial effects and EGF mRNA expression in salivary glands and gastric mucosa. Cigarette smoke delayed gastric ulcer healing and reduced cell proliferation, angiogenesis, and mucus synthesis. Exogenous EGF (10 and 20 microg/kg i.v.) before smoke exposure reversed the adverse effects of cigarette smoke, whereas vascular endothelial growth factor level and nitric oxide synthase activity were unaffected. It is concluded that the detrimental effect of cigarette smoke on ulcer healing is a consequence of reduction of angiogenesis, cell proliferation, and mucus secretion through the depressive action on EGF biosynthesis and its mRNA expression in salivary glands and gastric mucosa.
...
PMID:Reduction of EGF is associated with the delay of ulcer healing by cigarette smoking. 1064 56

We measured the concentrations of vascular endothelial growth factor (VEGF), nitric oxide and endothelin-1 (ET-1) in the gastric mucosa and examined the relationships between these factors. VEGF, nitric oxide and ET participate in angiogenesis and vascular remodeling, important elements of gastric ulcer healing. We studied cases of gastric ulcer as confirmed by endoscopic examination. All 61 cases in the angulus were positive for Helicobacter pylori (Hp). Fifteen cases were active stage (GA), 23 were healing stage (GH), and 23 were scarring stage (GS). As control, 17 cases of Hp-positive gastritis (gast+) and 14 cases of Hp-negative gastritis (gast-) were studied. Biopsy samples taken from the angulus during endoscopic examination were frozen and sliced into thin sections. ET was measured by enzyme immunoassay, VEGF was measured by enzyme-linked immunosorbent assay (ELISA) and nitric oxide was measured in terms of metabolite oxides of nitrogen (NOx) as described by Griess. ET, VEGF and inducible nitric oxide synthase (iNOS) were immunostained. The GA group had the highest concentration of NOx, suggesting that nitric oxide participates in the early stage of mucosal repair. In the GH group, all three factors showed high concentrations, suggesting that all may be involved in increased production. In the GS group, all three factors were significantly lower than in the GA and GH groups. Immunohistochemical studies showed that the distribution of ET- and iNOS-positive cells differed according to the ulcer stage. In particular, ET- and iNOS-positive cells in the vascular wall were primarily endothelial cells during GA and GH and vascular smooth muscle cells (VSMCs) during GS. These findings suggest that endothelial cells produce increased amounts of ET, nitric oxide and VEGF early in ulcer healing, a period of active endothelial cell repair and angiogenesis. During the scarring stage, vascular remodeling may result from the effects of ET and nitric oxide in regulating the proliferation of VSMCs. Our results suggest that VEGF. nitric oxide and ET participate in angiogenesis, vascular remodeling and mucosal regeneration during ulcer healing.
...
PMID:Changes of nitric oxide and growth factors during gastric ulcer healing. 1107 99

Bleeding and delayed healing of ulcers are well recognized clinical problems associated with the use of aspirin and other nonsteroidal antiinflammatory drugs, which have been attributed to their antiaggregatory effects on platelets. We hypothesized that antiplatelet drugs might interfere with gastric ulcer healing by suppressing the release of growth factors, such as vascular endothelial growth factor (VEGF), from platelets. Gastric ulcers were induced in rats by serosal application of acetic acid. Daily oral treatment with vehicle, aspirin, or ticlopidine (an ADP receptor antagonist) was started 3 days later and continued for 1 week. Ulcer induction resulted in a significant increase in serum levels of VEGF and a significant decrease in serum levels of endostatin (an antiangiogenic factor). Although both aspirin and ticlopidine markedly suppressed platelet aggregation, only ticlopidine impaired gastric ulcer healing and angiogenesis as well as reversing the ulcer-associated changes in serum levels of VEGF and endostatin. The effects of ticlopidine on ulcer healing and angiogenesis were mimicked by immunodepletion of circulating platelets, and ticlopidine did not influence ulcer healing when given to thrombocytopenic rats. Incubation of human umbilical vein endothelial cells with serum from ticlopidine-treated rats significantly reduced proliferation and increased apoptosis, effects reversed by an antibody directed against endostatin. Ticlopidine treatment resulted in increased platelet endostatin content and release. These results demonstrate a previously unrecognized contribution of platelets to the regulation of gastric ulcer healing. Such effects likely are mediated through the release from platelets of endostatin and possibly VEGF. As shown with ticlopidine, drugs that influence gastric ulcer healing may do so in part through altering the ability of platelets to release growth factors.
...
PMID:Platelets modulate gastric ulcer healing: role of endostatin and vascular endothelial growth factor release. 1135 54

Nonsteroidal anti-inflammatory drugs (NSAIDs) such as aspirin, indomethacin (IND), ibuprofen and newer cyclooxygenase-2 selective NSAIDs (e.g. celecoxib) delay gastric ulcer healing partly through the inhibition of angiogenesis, but the molecular mechanisms involved are not fully elucidated. Effective angiogenesis is required for ulcer healing to supply oxygen and nutrients to the healing site. The early growth response factor (Egr-1) is a transcription factor, which is rapidly activated by a variety of extracellular signals or tissue injury and is important for angiogenesis to occur. This study aimed to determine whether indomethacin (IND) and/or the selective COX-2 inhibitor, NS-398, interfere with egr-1 gene expression in human microvascular endothelial cells (HMVEC) in response to vascular endothelial growth factor (VEGF) stimulation. HMVEC were treated with 0.5 mM IND or 100 microM NS-398 for 16 h, and then VEGF (10 ng/ml) or vehicle was added. Egr-1 mRNA and protein expression levels were determined by RT-PCR and Western-blotting, respectively. VEGF treatment caused a significant elevation of Egr-1 mRNA (261+/-21%, P<0.001) and protein expression (174+/-15%, P<0.01) vs. vehicle. IND pre-treatment significantly inhibited VEGF-induced Egr-1 mRNA expression by 29+/-4% (P<0.01) and protein expression by 41+/-8% (P<0.05). NS-398 inhibited VEGF-induced Egr-1 mRNA and protein expression by 23+/-3% and 35+/-4%, respectively (both P<0.01). Since transcriptional activation of egr-1 is responsible for expression of proteins involved in proliferation of endothelial cells essential for angiogenesis, these results provide a new mechanism for NSAIDs' interference with angiogenesis.
...
PMID:NSAIDs inhibit the activation of egr-1 gene in microvascular endothelial cells. A key to inhibition of angiogenesis? 1159 63

Endothelins (ETs) participate directly and indirectly in angiogenesis via ET receptors. During early fetal angiogenesis, vascular endothelial growth factor (VEGF) and its receptors kinase insert domain-containing receptor (KDR) and fms-like tyrosine kinase-1 (Flt-1) are required for the development of the systemic vasculature. In late angiogenesis, stromal-cell-derived factor (SDF-1) and its receptor CXC chemokine receptor 4 (CXCR4) act in an organ-specific manner to promote the formation and development of large blood vessels supplying the gastrointestinal tract. We studied the roles of these ligand receptors in angiogenesis during healing of gastric ulcers. We studied the following five groups, each consisting of ten cases of endoscopically confirmed gastric ulcer: active stage (GA), healing stage (GH) and scar stage (GS) of gastric ulcers located in the angulus; Helicobacter pylori (Hp)-positive gastritis (gast+); and Hp-negative gastritis (gast-). All cases in the ulcer groups were Hp-positive. The study materials consisted of frozen biopsy specimens of lesions arising in the angulus. ET-1 was measured by enzyme immunoassay. The other factors were assayed by reverse-transcription-PCR. The distributions of ET-1, ETA receptor (ETAR), SDF-1 and CXCR4 in the gastric mucosa were evaluated by enzyme immunoassay. ET-1 and ETAR reached peak levels during the GH (ET: P<0.05, ETAR: P<0.01). VEGF mRNA increased slightly during the GA, but did not differ significantly among the groups. KDR and Flt-1 levels were high during the GA, the level being significantly higher than those during the GH and GS (P<0.05). SDF-1 levels significantly decreased during the GH and GS compared with levels during the GA, and CXCR4 significantly increased during the GH and GS (P<0.01). On immunostaining, ET-1-positive cells and ETAR-positive cells were found in the endothelium, vascular smooth muscle and gastric epithelium, and CXCR4-positive cells were found in the endothelium and gastric epithelium during the GH and GS. Our results suggest that VEGF receptors are mainly expressed early in ulcer development and participate in the initial stage of angiogenesis. SDF-1 receptors and ETAR are primarily expressed during the GH and GS and are involved in vascular maturation and gastric mucosal regeneration during late angiogenesis.
...
PMID:Roles of angiogenic factors and endothelin-1 in gastric ulcer healing. 1219 43

Delayed gastric ulcer healing is a well recognized problem associated with the use of cyclooxygenase (COX) inhibitors. In contrast, NO-releasing COX inhibitors do not interfere with ulcer healing. These divergent effects may in part be due to differences in their effects on platelets, which are known to influence ulcer healing. Therefore, we compared the effects of a nonselective COX inhibitor (flurbiprofen), a nitric oxide-releasing COX inhibitor (HCT-1026), and a selective COX-2 inhibitor (celecoxib) on gastric ulcer healing, angiogenesis, and platelet/serum levels of vascular endothelial growth factor (VEGF) and endostatin. Gastric ulcers were induced in rats by serosal application of acetic acid. Daily treatment with the test drugs was started 3 days later and continued for 1 week. Celecoxib and flurbiprofen impaired angiogenesis and delayed ulcer healing, as well as increasing serum endostatin levels relative to those of VEGF. HCT-1026 did not delay ulcer healing nor impair angiogenesis, and also did not change the ratio of serum endostatin to VEGF. Incubation of human umbilical vein endothelial cells with serum from celecoxib- or flurbiprofen-treated rats resulted in suppressed proliferation and increased apoptosis, effects that were reversed by an antiendostatin antibody. These results demonstrate a previously unrecognized mechanism through which nonsteroidal antiinflammatory drugs can delay ulcer healing, namely, through altering the balance of anti- and proangiogenic factors in the serum. The absence of a delaying effect of HCT-1026 on ulcer healing may be related to the maintenance of a more favorable balance in serum levels of pro- and antiangiogenic growth factors.
...
PMID:Divergent effects of new cyclooxygenase inhibitors on gastric ulcer healing: Shifting the angiogenic balance. 1223 50

Gastric mucosa of diabetic rats is highly vulnerable to acute injury, but little is known about the influence of diabetic conditions on the healing of gastric ulcers. In this study, streptozotocin (70 mg/kg injected intraperitoneally) was used to induce diabetes mellitus in rats. Four weeks after streptozotocin injection, gastric ulcers were induced using the acetic acid method, and 10 days later, the healing rate and the gastric blood flow (GBF) were measured by planimetry and hydrogen (H(2))-gas clearance method, respectively. Six major groups of rats with gastric ulcers were used: (1) vehicle (saline); (2) streptozotocin alone; (3) insulin (4 IU/day intraperitoneally); (4) streptozotocin plus insulin; (5) pentoxifylline, an inhibitor of synthesis and release of tumor necrosis factor-alpha (TNF alpha); and (6) aspirin, a non-selective inhibitor of cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2), and rofecoxib, the highly selective COX-2. In the diabetic rats, a significant delay in ulcer healing ( approximately by 300%), accompanied by a decrease in the gastric mucosal blood flow was observed. The prolongation of the healing in diabetic animals was associated with an increase in gastric mucosal expression and release of TNFalpha, interleukin-1 beta (IL-1 beta), suppression of the vascular endothelial growth factor (VEGF), platelet endothelial cell adhesion molecule-1 (PECAM-1) and the mucosal overexpression of heat shock protein 70 (HSP 70). Administration of insulin reversed the delay in ulcer healing and significantly decreased the expression of IL-1 beta and TNF-alpha, while producing the rise in the expression of VEGF and PECAM. Pentoxifylline, an inhibitor of TNF-alpha, which by itself accelerated ulcer healing in non-diabetic rats, counteracted the increase in the area of gastric ulcer induced by streptozotocin, raised significantly gastric blood flow and suppressed the plasma TNF-alpha levels. Aspirin and rofecoxib, that significantly suppressed the mucosal prostaglandin E(2) generation in ulcer area, delayed significantly the rate of ulcer healing and decreased the GBF at ulcer margin in non-diabetic rats, and these changes were significantly augmented in diabetic animals. We conclude that: (1) Experimental diabetes dramatically impairs ulcer healing, depending upon the increased release of proinflammatory cytokines and the attenuation of angiogenesis that can limit the ulcer healing effects of locally produced HSP 70 and TNF-alpha. (2) Insulin reversed this impairment of ulcer healing in diabetic rats, mainly due to the enhancement of angiogenesis and reduction in expression of cytokines in the ulcer area. (3) Classic non-steroidal anti-inflammatory drugs such as aspirin prolonged ulcer healing under diabetic conditions due to suppression of endogenous prostaglandins and the fall in the microcirculation at the ulcer margin and these effects were mimicked by selective, so called "safe" COX-2 inhibitor, rofecoxib, suggesting that both COX isoforms are important sources of prostaglandins that are essential in the ulcer healing in diabetes.
...
PMID:Impaired gastric ulcer healing in diabetic rats: role of heat shock protein, growth factors, prostaglandins and proinflammatory cytokines. 1464 93

Using the non-ulcerogenic doses of dexamethasone, we explored the action of glucocorticoids on ulcer healing and its relationship with angiogenic factors in the gastric mucosa. We applied dexamethasone (0.1 or 0.2 mg/kg/day) intragastrically in rats with acetic acid-induced gastric ulcer. The mucosal prostaglandin E(2) level and protein expressions of basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) at the ulcer margin were determined. Ulcer induction significantly increased protein expressions of bFGF, VEGF, and prostaglandin E(2) level at the ulcer margin together with angiogenesis at the ulcer margin and base. The non-ulcerogenic doses of dexamethasone inhibited angiogenesis at the ulcer margin and ulcer base and delayed ulcer healing. These were associated with a significant decrease of prostaglandin E(2) level and VEGF expression, but not the bFGF expression. Supplementation with prostaglandin E(2) attenuated the inhibitory action of dexamethasone on VEGF expression and reversed the adverse effects of dexamethasone on angiogenesis and ulcer healing, without influencing bFGF expression. We concluded that dexamethasone given at non-ulcerogenic doses could decrease angiogenesis and delay acetic acid-induced ulcer healing; these actions were at least, in part, due to depletion of prostaglandin E(2) level followed by down-regulation of VEGF at the ulcer margin of the stomach.
...
PMID:Dexamethasone delays ulcer healing by inhibition of angiogenesis in rat stomachs. 1475 51

1 2 3 4 Next >>