Role of Epidermal Growth Factor (EGF) in Oesophageal Mucosal Integrity

Abstract

Oesophageal mucosa has well established protective mechanisms, which operate within pre-epithelial, epithelial and post-epithelial compartments. Since refluxed acid and pepsin always act from the luminal side of the mucosa, protective factors like EGF, operating as a part of pre-epithelial defence, are thought to be pivotal in the maintenance of the integrity of the oesophageal mucosa. The significant contribution of salivary EGF to the quality of the oesophageal mucosal barrier has been demonstrated in an experimental setting and in a clinical scenario. Patients with low salivary EGF levels are predisposed to severe oesophageal damage if they develop gastro-oesophageal reflux and are a high-risk group for development of Barrett's oesophagus. Not only the salivary glands but also the human oesophagus has a profound ability to elaborate and release EGF. Some changes in luminal release of EGF during oesophageal mucosal exposure to intraluminal damaging factors imply its role in the oesophageal protective mechanisms. To exert biological effects within the oesophageal mucosal compartment, EGF requires binding to the ligand-binding domain of its receptor. This process results in receptor dimerisation, autophosphorylation and activation of intracellular signal transduction pathways. EGF receptors are localised on the basolateral and luminal aspect of the mucosal cells playing an important role in fast regeneration of oesophageal epithelium through the high mitotic activity of its proliferative zone. An increase in the rate of salivary EGF secretion during masticatory stimulation suggests its potential therapeutic benefit in the treatment of patients with damaged oesophageal mucosa.

IGFBP-3 and IGFBP-10 (CYR61) up-regulation during the development of Barrett's oesophagus and associated oesophageal adenocarcinoma: potential biomarkers of disease risk

“…Interestingly, a recent study has suggested that IGFBP-3 up-regulation in oesophageal cells may be mediated by the epithelial growth factor receptor (EGFR) (Takaoka et al 2004). Epithelial growth factor (EGF) signalling is known to play a crucial role in oesophageal healing (Marcinkiewicz et al 1998), supporting, therefore, our hypothesis that IGFBPs expression may be part of the physiological response to epithelial damage.…”

Estudo comparativo da concentração salivar do fator de crescimento epidérmico em indivíduos com laringite crônica por doença do refluxo gastroesofágica antes e após o tratamento: resultados preliminares

“…out before the present one, have established salivary and digestive tract deficiencies of protection factors, such as EGF, in individuals with dyspeptic disease or reflux esophagitis 21,22,25,26 . More recently we have established a significant reduction in EGF salivary concentration in individuals with GERD chronic laryngitis when compared to a group of normal individuals 15,16,27 .…”

“…One of the factors most responsible for homeostasis of the oral mucosa and the digestive tract is the saliva and its organic content. The Epidermal Growth Factor -EGF, is the salivary protein with the most action on epithelial regeneration after physical and chemical aggression, because of its important capacity in replicating DNA and aiding in the neoangiogenesis of epithelial cells 25 . In a recent study, we proved that there is a significant EGF concentration reduction in saliva in individuals with LPR when compared to normal individuals 27 .…”

“…Certainly, the gastric and esophageal mucosal protection mechanisms have a decisive role in the capacity these organs have of withstanding mechanical and chemical aggression to which they are daily exposed, and many of these mechanisms are saliva-mediated 15,[20][21][22][23][24][25][26][27] . Saliva has many organic and inorganic substances that contribute to this protection against physical and chemical attacks, and used for the maintenance of the mucosal lining, not only of the oral mucosa, but also that of the digestive tract20-26.…”

Pathogenese von Barrett-Ösophagus und Barrett-Karzinom

“…Ein anderer Wachstumsfaktor, «acidic fibroblast growth factor» (aFGF) akkumuliert während der Progression von der Metaplasie zum Karzinom [46]. Andererseits tragen Wachstumsfaktoren auch zum Schutz vor gastroösophagealem Reflux und zur mukosalen Barriere im Ösophagus bei, wie zum Beispiel EGF aus Speichel und Öso-phagusepithel [47]. Welches Equilibrium in der Expression von Wachstumsfaktoren und deren Rezeptoren physiologisch erforderlich ist, ist noch ungeklärt.…”