transforming-growth-factor-alpha and Gastroesophageal-Reflux

Functional oesophageal epithelial defense, including cell proliferation, restitution, buffers and ion transporters, plays a significant role in maintaining mucosal integrity and enabling rapid repair after injury. Growth factors such as epidermal growth factor (EGF), transforming growth factor-alpha (TGF-alpha), hepatocyte growth factor (HGF) and keratinocyte growth factor (KGF) are associated with oesophageal epithelial proliferation or restitution. Na+/H+ exchanger-1, an ion transporter, regulates intracellular pH and cell volume, and may have roles in cell proliferation, migration and survival. Cytokine, adhesion molecules, cyclooxygenase-2 and free radicals are associated with oesophageal inflammation and breach of the functional epithelial defense. Although the oesophagus does not have strong functional epithelial defense against acid, this defensive mechanisms may be involved in the pathogenesis of non-erosive gastro-oesophageal reflux disease. Medical therapy may be developed in future to enhance functional oesophageal epithelial defense.

Topics: Cell Proliferation; Epithelial Cells; Esophagus; Gastric Acid; Gastroesophageal Reflux; Humans; Immunohistochemistry; Transforming Growth Factor alpha

It has been previously demonstrated that patients with reflux esophagitis exhibit a significant impairment in the secretion of salivary protective components versus controls. However, the secretion of salivary protective factors in patients with nonerosive reflux disease (NERD) is not explored. The authors therefore studied the secretion of salivary volume, pH, bicarbonate, nonbicarbonate glycoconjugate, protein, epidermal growth factor (EGF), transforming growth factor alpha (TGF-α) and prostaglandin E2 in patients with NERD and compared with the corresponding values in controls (CTRL).. Salivary secretion was collected during basal condition, mastication and intraesophageal mechanical (tubing, balloon) and chemical (initial saline, acid, acid/pepsin, final saline) stimulations, respectively, mimicking the natural gastroesophageal reflux.. Salivary volume, protein and TGF-α outputs in patients with NERD were significantly higher than CTRL during intraesophageal mechanical (P < 0.05) and chemical stimulations (P < 0.05). Salivary bicarbonate was significantly higher in NERD than CTRL group during intraesophageal stimulation with both acid/pepsin (P < 0.05) and saline (P < 0.01). Salivary glycoconjugate secretion was significantly higher in the NERD group than the CTRL group during chewing (P < 0.05), mechanical (P < 0.05) and chemical stimulation (P < 0.01). Salivary EGF secretion was higher in patients with NERD during mechanical stimulation (P < 0.05).. Patients with NERD demonstrated a significantly stronger salivary secretory response in terms of volume, bicarbonate, glycoconjugate, protein, EGF and TGF-α than asymptomatic controls. This enhanced salivary esophagoprotection is potentially mediating resistance to the development of endoscopic mucosal changes by gastroesophageal reflux.

Topics: Adult; Dinoprostone; Epidermal Growth Factor; Female; Gastroesophageal Reflux; Humans; Hydrogen-Ion Concentration; Male; Middle Aged; Physical Stimulation; Saliva; Salivary Elimination; Salivary Glands; Sodium Chloride; Stimulation, Chemical; Transforming Growth Factor alpha