epidermal-growth-factor and Esophagitis

There has been much interest in recent years in the potential protective role of saliva in the esophagus. Variables such as salivary volume and neutralizing capacity have been studied both during basal conditions and in response to esophageal acid exposure, in healthy subjects and in patients with esophagitis. In addition to its known neutralizing capacity, saliva also contains growth factors. These polypeptides (of which epidermal growth factor has been studied most) have cytoprotective and healing properties in various segments of the gastrointestinal tract. Therefore, a deficiency in one or more of these growth factors might be a contributing factor in the development of gastroesophageal reflux disease (GERD) or its complication, such as Barrett's metaplasia. However, human studies have produced contradictory results regarding salivary growth factor deficiency in such patients. Current methods of investigation make it difficult to assess the importance of saliva in GERD. This may be due in part to the multifactorial nature of the disease and the difficulty in long-term, selective manipulation of salivary function in humans. Given the present data in the literature, it is therefore unknown if saliva plays an important role in esophageal protection.

Topics: Acids; Animals; Barrett Esophagus; Epidermal Growth Factor; Esophagitis; Esophagus; Growth Substances; Humans; Reference Values; Saliva

To establish and characterize radiation-induced esophagitis (RIE) in vivo and in vitro.. Fractionated thoracic irradiation at 0, 8, 12, or 15 Gy was given daily for 5 days to Balb/c or C57Bl/6 mice. Changes in body weight gain and daily food intake were assessed. At the end of the study, we removed the esophagus and examined histology by hematoxylin and eosin staining, immune cell infiltration and apoptosis by fluorescence-activated cell sorting, and gene expression changes by quantitative real-time polymerase chain reaction. Het-1A human esophageal epithelial cells were irradiated at 6 Gy, treated with recombinant human growth factors, and examined for gene expression changes, apoptosis, proliferation, and signal transduction pathways.. We observed that irradiation at 12 Gy or 15 Gy per fraction produced significant reduction in body weight and decreased food intake in Balb/c mice but not as much in C57Bl/6 mice. Further analyses of Balb/c mice irradiated at 12 Gy/fraction revealed attenuated epithelium, inflamed mucosa, and increased numbers of infiltrating CD4+ helper T cells and apoptotic cells. Moreover, we found that expression of tissue inhibitor for metalloproteinase-1, plasminogen activator inhibitor-1, granulocyte macrophage-colony stimulating factor, vascular endothelial growth factor, and stromal-derived factor-1 were increased, whereas epidermal growth factor (EGF) was decreased. Irradiated Het-1A cells similarly showed a significant decrease in expression of EGF and connective tissue growth factor (CTGF). Treatment of EGF but not CTGF partially protected Het-1A cells from radiation-induced apoptosis and revealed phosphorylation of EGFR, AKT, and ERK signaling pathways.. We established a mouse model of RIE in Balb/c mice with 12 Gy × 5 fractions, which showed reduced body weight gain, food intake, and histopathologic features similar to those of human esophagitis. Decreased EGF expression in the irradiated esophagus suggests that EGF may be a potential therapeutic intervention strategy to treat RIE.

Topics: Animals; Cell Line, Tumor; Dose-Response Relationship, Radiation; Epidermal Growth Factor; Esophagitis; Humans; Male; Mice; Mice, Inbred BALB C; Radiation Injuries; Radiotherapy Dosage; Treatment Outcome

Although the pathogenesis and treatment of erosive esophagitis (EE) is well recognized, little is known about the cellular and molecular mechanisms of mucosal healing in EE patients. In this pilot study, we enrolled typical EE patients to evaluate what kinds of growth factors and their receptors were activated in their injured esophageal mucosa. Forty endoscopically proved EE patients were consecutively enrolled. Messenger RNA expressions, which includes keratinocyte growth factor (KGF) and its receptor (KGFR), epidermal growth factor (EGF) and its receptor (EGFR), hepatocyte growth factor (HGF) and its receptor (HGFR), basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF), and cyclooxygenase (COX)-1 and COX-2, were measured using real-time polymerase chain reaction (PCR). Data were compared between the injured EE mucosa and their normal esophageal mucosa above EE. The mRNA expressions of HGF, HGFR, EGF, VEGF, and COX-2, but not EGFR, KGF, KGFR, bFGF, and COX-1, were significantly increased in the injured mucosa of EE patients compared with those of normal mucosa (P < 0.05). The study found that HGF, HGFR, EGF, VEGF, and, COX-2 are activated in the injured mucosa of EE patients; their activation might be involved in mucosal repair and ulcer healing of EE.

Topics: Adult; Aged; Cyclooxygenase 1; Cyclooxygenase 2; Epidermal Growth Factor; ErbB Receptors; Esophagitis; Female; Fibroblast Growth Factor 7; Gene Expression Profiling; Gene Expression Regulation; Hepatocyte Growth Factor; Humans; Intercellular Signaling Peptides and Proteins; Male; Middle Aged; Proto-Oncogene Proteins c-met; Receptor, Fibroblast Growth Factor, Type 2; RNA, Messenger; Vascular Endothelial Growth Factor A

Erosive esophagitis frequently develops after successful Helicobacter pylori eradication. Since salivary secretion of epidermal growth factor (EGF) plays a crucial role in the pathogenesis of gastroesophageal reflux disease, the current study objective was to find out whether erosive esophagitis development after Helicobacter pylori eradication is associated with the secretion of EGF in saliva.. A total of 115 H. pylori infected patients (positive results of CLO-test, histology and serology) with a duodenal ulcer were recruited for the study. Gastroscopic examinations and saliva collections were performed twice, prior to H. pylori eradication and one year after its cessation. The salivary EGF was determined using a radioimmunological method.. Salivary EGF secretion was lower in H. pylori infected subjects with erosive esophagitis than without (0.82+/-0.66 vs 1.70+/-3.49 ng/min, p=0.021). However, a year after successful H. pylori eradication, salivary EGF did not differ between the groups (2.17+/-2.06 vs 1.79+/-2.06 ng/min); the lack of difference was due to high peptide secretion in patients who developed erosive esophagitis after eradication.. Erosive esophagitis development following H. pylori eradication is not the result of decreased salivary EGF secretion.

Topics: Adolescent; Adult; Aged; Duodenal Ulcer; Epidermal Growth Factor; Esophagitis; Female; Follow-Up Studies; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Saliva; Young Adult

Secretion of salivary protective factors in patient s with gastroesophageal reflux disease is impaired. However, the impact of physiological stimulus mastication on salivary protective factors output remains largely unknown. The aim of this study was to measure salivary volume, pH, HCO3-, peptide growth factors, prostaglandin, mucin, protein, and viscosity during mastication.. In 31 asymptomatic volunteers and 36 patients with endoscopic reflux esophagitis, in basal and parafilm chewing-stimulated saliva, its volume, pH, bicarbonate, epidermal growth factor, transforming growth factor alpha, prostaglandin E2, mucin, protein, and viscosity were investigated.. Masticatory stimulation in controls resulted in a significantly increased salivary volume by 205%, pH by 7.6%, bicarbonate by 335%, mucin by 137%, protein by 98%, epidermal growth factor by 123%, and prostaglandin E2 by 132%, accompanied by an increase in transforming growth factor alpha by 80% with 19% decline in viscosity vs. basal values. Mastication in reflux esophagitis significantly increased salivary volume by 215%, pH by 6.8%, bicarbonate by 257%, mucin by 135%, protein by 94%, epidermal growth factor by 207%, and prostaglandin E2 by 240%, whereas transforming growth factor alpha increased by 225% and viscosity by 64% when compared with corresponding basal values.. A profound and significant increase in the secretion rate of inorganic and organic protective components in saliva during masticatory stimulation suggests its potential value as a therapeutic approach to the treatment of patients with gastroesophageal reflux disease.

Topics: Adult; Aged; Bicarbonates; Dinoprostone; Epidermal Growth Factor; Esophagitis; Female; Gastroesophageal Reflux; Humans; Hydrogen-Ion Concentration; Male; Mastication; Middle Aged; Mucins; Saliva; Salivary Proteins and Peptides; Viscosity

Our objective was to investigate the putative role of epidermal growth factor (EGF) in esophagitis pathogenesis in both nondrinkers and chronic alcoholics. We studied the EGF serum level, the EGF salivary concentration, and the esophageal EGF receptor expression in different groups of patients with esophagitis: nondrinkers with typical symptoms of gastroesophageal reflux (N = 12) and chronic alcoholics (N = 12), and in controls: chronic alcoholics without esophagitis (N = 16) and healthy nondrinkers (N = 12). All patients had an endoscopy with esophageal biopsies, 24-hr esophageal pH-metry, and esophageal manometry. EGF serum levels and EGF salivary concentrations were determined by radioimmunoassay. EGF receptor expression was determined by immunohistochemistry. Both the EGF serum level and the EGF salivary concentration remained constant, 328 +/- 21 pg/ml and 305 +/- 48 pg/ml, respectively, regardless of alcohol intake and the presence or absence of esophagitis. In addition, the presence of esophagitis did not affect the EGF receptor expression. These results suggest that seric and salivary EGF is not involved in the pathogenesis of reflux esophagitis in nondrinkers and in chronic alcoholics.

Topics: Adult; Alcoholism; Epidermal Growth Factor; ErbB Receptors; Esophagitis; Esophagitis, Peptic; Esophagus; Female; Gastroesophageal Reflux; Humans; Hydrogen-Ion Concentration; Immunohistochemistry; Male; Manometry; Middle Aged; Monitoring, Physiologic; Prospective Studies; Radioimmunoassay; Saliva

Epidermal growth factor (EGF) has been implicated in mitogenesis and oncogenesis in the gastrointestinal tract. To determine the role of EGF in oesophageal disease, its quantity and distribution in the oesophageal mucosa of control subjects and patients with oesophageal disease were studied. Oesophageal biopsy specimens, taken 20-40 cm from the incisors in 72 patients, were graded histologically and adjacent specimens were taken for immunohistochemical analysis of the distribution of EGF. In patients with Barrett's columnar lined oesophagus, specimens were also taken from the gastric cardia for comparison. Twenty two biopsy specimens showed oesophagitis, 20 Barrett's mucosa, and 30 were histologically normal. EGF was found in the capillary endothelium of the normal oesophageal papillae and basal mucosa. Significantly more EGF positive papillae were found in the normal mucosa (81%) than in the inflamed mucosa (42%) (p < 0.001). The 20 patients with Barrett's mucosa showed abnormal expression of EGF in 25% of the isthmus and superficial epithelial cells. This study has shown that EGF is found only in the endothelial cells of the capillaries of the normal oesophageal mucosa and that the peptide is detectable significantly less frequently than normal in the inflamed oesophageal mucosa. EGF is also abnormally present, in large quantities, in the cytoplasm of the epithelial cells of Barrett's mucosa compared with gastric mucosa.

Topics: Adult; Aged; Aged, 80 and over; Barrett Esophagus; Cardia; Endothelium, Vascular; Epidermal Growth Factor; Epithelium; Esophageal Diseases; Esophagitis; Esophagus; Female; Gastric Mucosa; Humans; Immunohistochemistry; Male; Middle Aged; Mucous Membrane

Topics: Arthritis, Rheumatoid; Epidermal Growth Factor; Esophagitis; Female; Humans; Middle Aged; Salivary Glands