Role of salivary epidermal growth factor in the maintenance of physicochemical characteristics of oral and gastric mucosal mucus coat

doi:10.1016/S0006-291X(88)80444-3

Biochemical and Biophysical Research Communications

Volume 152, Issue 3, 16 May 1988, Pages 1421-1427

https://doi.org/10.1016/S0006-291X(88)80444-3 Get rights and content

Summary

The involvement of salivary epidermal growth factor (EGF) in the maintenance of oral and gastric mucosal mucus coat dimension and chemical characteristics was investigated using sialoadenectomized rats. Examination of the oral and gastric mucosal surface by phase contrast microscopy and Alcian blue uptake revealed that deprivation of salivary EGF caused a 31–36% reduction in mucus coat thickness and a 38–43% reduction in adherent mucin content. Chemical analyses indicated that the mucus coat of sialoadenectomized group exhibited a 21–28% increase in protein and a 67% decrease in covalently bound fatty acids, a 30% decrease in carbohydrates, and a 32–37% decrease in lipids. Sialoadenectomy also evoked changes in the chemical composition of mucus glycoprotein component of oral and gastric mucus coat reflected in the lower content of sulfate (25–26%), associated lipids (24–25%), and covalently bound fatty acids (67–75%). Intragastric supplementation of EGF had no effect on the physicochemical changes caused by sialoadenectomy in the oral mucosal mucus coat, while nearly complete restoration to normal characteristics occurred in the gastric mucosal mucus coat. The results suggest that salivary EGF is essential for the maintenance of mucus coat dimension and quality needed in the protection of alimentary tract epithelium.

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Cited by (86)

A novel approach to describing the pancreas and submandibular gland: Can they be classified as primary and secondary tissue organs?
2022, Acta Histochemica
Citation Excerpt :
For example, removing SMGs in rats exacerbated ethanol induced gastric ulcers (Leitch, 1985) and showed higher susceptibility to ulcerogenic agents such as dexamethasone and indomethacin (Olsen et al., 1986). In addition to EGF, mucins and other proteins secreted from SMGs aid the healing of an ulcer (Skinner et al., 1984; Olsen et al., 1986; Sarosiek et al., 1988). During the healing process, salivary and pancreatic progenitors also share a very similar mechanism in repair and regeneration (Mathison, 2010).
Our aim is to examine the relationship between the submandibular gland (SMG) and the pancreas by discussing similarities and differences in their embryology, histology, physiology, and pathology, and to introduce the question of classifying them as primary or secondary organs. From an embryonic standpoint, SMG and pancreas originate from different germ layers, yet they share a variety of similar elements in their morphogenesis, branching process, and mesenchymal molecular interaction. The histological and anatomical comparison between these two organs reveals parallels in the basic function of their exocrine physiology. With both the SMG and pancreas playing a significant role in digestive processes, there are also common aspects in their exocrine function. Furthermore, recent research has unraveled an intricate novel system of hormonal interaction between the salivary glands and pancreas which regulates pancreatic cellular differentiation and injury repair mechanism. Lastly, there are analogous features in the pathological mechanisms and inflammatory processes in the course of chronic disease in both organs. By defining this close relationship between the SMG and the pancreas, we aim to provide alternative insights for scholars and physicians in the shared characteristics of basic function of these organs, and possible pathological consequences of their dysregulation.
The impact of Helicobacter pylori on EGF, EGF receptor, and the c-erb-B2 expression
2014, Advances in Medical Sciences
Citation Excerpt :
Recent data suggest that increased expression of epidermal growth factor (EGF) and its receptor (EGFR), and expression of homological EGF receptor – c-erb-B2 protein in gastric mucosa may induce changes in gastric epithelial cells leading to cancer [5–11]. EGF, through interaction with its receptor, stimulates the cell proliferation and migration and triggers epithelial cell signaling [12,13]. A few studies have shown that H. pylori infection is associated with increased EGF expression, and with up-regulation of EGFR expression, which has an antiapoptotic effect on gastric epithelial cells [14–20].
Increased expression of epidermal growth factor (EGF), its receptor (EGFR), and c-erb-B2 protein, which is homological with the EGF receptor, in gastric mucosa, may play a role in gastric carcinogenesis. We assessed if the infection and eradication of Helicobacter pylori (H. pylori) affects the gastric expression of growth factors and serum gastrin concentrations.
We examined immunohistochemically gastric EGF and both receptors’ expression in: gastric cancer (GC; n = 29), chronic gastritis with H. pylori infection (GHp+; n = 40) before and after eradication and in patients without H. pylori infection (GHp−; n = 42).
Before the eradication therapy, gastric mucosal EGF and both receptor's expressions in GHp+ patients were increased compared to GHp− (p < 0.05), but were similar to GC. After eradication, EGF and the receptor's expression significantly decreased in the gastric body. Both EGFR and c-erb-B2 expression in the antrum were still higher than in GHp− (p < 0.05), and remained comparable to GC.
In patients with H. pylori infection the gastric mucosal EGF, EGFR, and c-erb-B2 expressions are similar to those observed in gastric cancer. The persistence of the antral expression of receptors after eradication, at a level comparable to the gastric cancer group, suggests their eventual role in the progression of changes initiated by H. pylori toward carcinogenesis.
A distinct salivary secretory response mediated by the esophago-salivary reflex in patients with Barrett's esophagus: Its potential pathogenetic implications
2014, Advances in Medical Sciences
Citation Excerpt :
Proteins such as proline-rich proteins, fucose-rich glycoprotein, histidine-rich proteins have been found to play a significant role in the maintenance of the integrity of the oral cavity mucosa [30,34–38]. The protective role of EGF is related to esophageal and gastric mucosal repair of the damage in the alimentary tract [39,40]. Overall our current study indicates that patients with BE exhibit a significant impairment in salivary secretory function, mediated by esophago-salivary reflex evoked by intraesophageal mechanical and chemical stimulation, mimicking the natural gastroesophageal reflux scenario.
A significantly compromised epidermal growth factor (EGF) secretion by basal parotid saliva may contribute to the development of Barrett's esophagus (BE). The rate of secretion of EGF as well as a wide spectrum of protective factors in total basal and stimulated saliva in BE patients remains to be explored. We therefore studied the rate of secretion of salivary buffers, glycoconjugate, protein, EGF, transforming growth factor α (TGFα) and prostaglandin E₂ (PGE₂), evoked by esophago-salivary reflex, in patients with BE and controls (CTRL).
Salivary secretion was collected during basal condition, mastication, and intraesophageal mechanical and chemical stimulations respectively, mimicking the natural gastroesophageal reflux scenario.
Salivary pH in BE was significantly lower than in controls during mechanical (p < 0.001) and chemical stimulations (p < 0.001). Bicarbonate and protein outputs in BE were significantly lower during mechanical (p < 0.05) and chemical stimulations (p < 0.01). The non-bicarbonate and glycoconjugate outputs in BE were lower during chemical stimulation (p < 0.05) and during mechanical (p < 0.05) and chemical stimulations (p < 0.05) respectively. The rate of salivary EGF output in BE was significantly lower during mechanical stimulation (p < 0.05). We observed a higher TGFα output during mastication (p < 0.05) and PGE₂ secretion during basal and masticatory condition (p < 0.05) in BE.
Patients with BE demonstrated significantly compromised salivary pH and rate of secretion of bicarbonate, non-bicarbonate, glycoconjugate, protein and EGF. This impairment could potentially predispose to the development of accelerated esophageal mucosal injury. Potential restoration of this impairment by masticatory stimulation of salivary secretion using sugarless chewing gum justifies further clinical exploration.
Morphological changes and EGF expression in the granular convoluted tubule cells of submandibular glands of Trypanosoma cruzi infected rats
2008, Tissue and Cell
We have previously demonstrated in rats that Chagas’ disease affects the salivary glands, by promoting an enlargement of the submandibular gland. In order to further investigate possible functional alterations on infected submandibular glands, the objective of the present study was to analyze epidermal growth factor (EGF) expression on rat submandibular glands during Trypanosoma cruzi infection. Results demonstrated that infected rats presented lower levels of testosterone, and morphological changes in the granular convoluted tubule (GCT) cells of the submandibular glands, along with acinar enlargement and delayed ductal maturation at the developing granular ducts. Immunohistochemistry analysis additionally showed that only few cells immunolabelled with anti-EGF on infected rats during the acute phase of Chagas’ disease, while after 64 and 90 days (chronic phase) of infection, EGF expression was similar to non-infected rats. The present findings suggest that at the acute phase of Chagas’ disease, lower levels of testosterone may lead to a delayed maturation of GCT, which positively correlates with decreased EGF production by submandibular glands cells.
Significant Enhancement of Esophageal Pre-Epithelial Defense by Tegaserod: Implications for an Esophagoprotective Effect
2007, Clinical Gastroenterology and Hepatology
Citation Excerpt :
Protective components of secretions such as buffers, and mucin have an immediate effect, neutralizing the digestive power of gastroesophageal refluxate and acting through the mucus/buffer layer covering the esophageal mucosa.11 Other protective components, such as EGF and TGFα, have a long-term role in the surveillance of the mucosal integrity and repair should any injury take place.12,33–36 We recently showed that GERD patients with RE show significantly lower EGF in salivary and esophageal secretions.15,16
Background & Aims: Tegaserod, a serotonin 5-hydroxytryptamine (5-HT)₄ receptor agonist, is thought to stimulate intestinal secretions. The aim of the current study was to assess the effect of tegaserod vs placebo on salivary and esophageal protective factors in patients with gastroesophageal reflux disease (GERD). Methods: This study was a randomized, double-blind, placebo-controlled, cross-over trial in 38 GERD patients treated with tegaserod 6 mg twice a day vs placebo. Salivary samples were collected basally and during mastication. In addition, in 32 GERD patients, salivary and esophageal secretions also were collected during infusion of NaCl, HCl/pepsin, and NaCl in a consecutive fashion using a specially designed esophageal catheter. Saliva and esophageal perfusates were assessed for the pH, volume, content of buffers, protein, mucin, epidermal growth factor (EGF), transforming growth factor α (TGFα), and prostaglandin E (PGE)₂ and analyzed statistically. Results: Salivary flow rates during administration of tegaserod increased over corresponding values during both basal conditions (P < .01) and mastication (P < .001). The rate of secretion of salivary bicarbonate and nonbicarbonate buffers also increased in basal conditions (P < .001 and P < .01, respectively) and during mastication (P < .05 and P = .05). Salivary EGF increased during mastication (P < .05), whereas PGE₂ and TGF α increased in basal conditions (P < .05 and P < .01). Esophageal perfusate volumes increased during administration of tegaserod in basal conditions (P < .05), whereas esophageal EGF secretion increased after mucosal exposure to HCl/pepsin and subsequent final perfusion with NaCl (P < .05). Conclusions: Significant stimulatory impact of 5-HT₄ agonist on several salivary protective factors as well as esophageal EGF secretion may have esophagoprotective implications in patients with GERD and may help to address new therapies in the future.
The sequential cleavage of membrane anchored pro-EGF requires a membrane serine protease other than kallikrein in rat kidney
2004, Regulatory Peptides
Epidermal growth factor (EGF) is present in kidney membranes as an integral type I precursor protein, enzymatically processed to release immunoreactive materials in urine or incubation medium. The aim of this work was the elucidation of both the anchor of the serine protease activity that processes pro-EGF, and the determination of the steps of the enzymatic processing. Quantification of EGF containing molecules by RIA following gel filtration analysis demonstrated that the membrane precursor is first shed from the kidney membrane principally into a 170-kDa soluble precursor. This entire ectodomain is further processed into a 70-kDa precursor and finally into the mature 5.9 kDa urinary EGF. These species correspond to the ones found in urines. Both shedding and maturation events are clearly realized by membrane anchored serine protease activity, which remains active in detergent. By use of wild-type and knockout mice urines, we found that tissue kallikrein (TK) was not involved in the regulation of this processing.

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Role of salivary epidermal growth factor in the maintenance of physicochemical characteristics of oral and gastric mucosal mucus coat

Summary

Biochim. Biophys. Acta

Progr. Lipid Res.

Gastroenterology

Biochem. Pharmacol.

Arch. Biochem. Biophys.

J. Biol. Chem.

J. Biol. Chem.

Int. Rev. Cytol.

Biochim. Biophys. Acta

Biochim. Biophys. Acta

J. Oral Pathol.