Salivary Epidermal Growth Factor Research Articles

Decreased levels of salivary prostaglandin E 2 and epidermal growth factor in recurrent aphthous stomatitis

Prostaglandin E 2 and epidermal growth factor are two important cytoprottective compounds in saliva. This study investigated their salivary levels in controls and individuals with minor recurrent aphthous stomatitis. The development of recurrent aphthous stomatitis was divided into three stages: (1) early active stage (mucosal redness); (2) active stage (mucosal ulceration); (3) convalescent stage. Unstimulated mixed saliva was collected from each volunteer. Salivary prostaglandin E 2 and epidermal growth factor concentrations were determined by radioimmunoassay. Their levels (mean ± SEM) were significantly lower during the active stage of ulceration as compared to the control: (a) for prostaglandin E 2, 200 ± 55 versus 73 ± 11 pg/mg salivary protein ( p < 0.01), 447 ± 123 versus 112 ± 19 pg/ml saliva ( p < 0.01), 215 ± 30 versus 63 ± 12 pg/min salivary flow ( p < 0.01), control ( n = 12) versus active stage ( n = 15); (b) for epidermal growth factor, 1.09 ± 0.17 versus 0.67 ± 0.17 ng/mg salivary protein ( p < 0.05); 2.51 ± 0.53 versus 0.84 ± 0.19 pg/ml saliva ( p < 0.05, 1.24 ± 0.26) versus 0.41 ± 0.09 pg/min salivary flow ( p < 0.05), control ( n = 12) versus active stage ( n = 12). Salivary prostaglandin E 2 and epidermal growth factor showed stage-dependent alterations during the development of the stomatitis. The prostaglandin E 2 concentration decreased significantly during the active stage of ulceration, and then increased significantly during the convalescent stage. However, the recovery of salivary epidermal growth factor after the ulceration was slower than that of the prostaglandin E 2. It is suggested that the diminution of prostaglandin E 2 and epidermal growth factor in the saliva may be associated with the ulcer development.

Do salivary organic components play a protective role in health and disease of the esophageal mucosa?

Aggressive factors operating within the esophageal lumen during gastroesophageal reflux are balanced by adequately mobilized protective mechanisms. Esophageal mucosal protection operates at three different although complementary dimensions: (1) preepithelial, (2) epithelial and (3) postepithelial. Since aggressive factors predominantly operate within the esophageal lumen, preepithelial defense is pivotal in mucosal protection. The preepithelial barrier is significantly enhanced by the quantity and the quality of salivary organic components such as salivary mucin, nonmucin protein, salivary epidermal growth factor (EGF) and salivary prostaglandin E2. The rate of secretion of salivary mucin, nonmucin protein and EGF under the impact of intraesophageal mechanical (bolus) and chemical (HCl/pepsin) stimulation, mimicking the natural gastroesophageal reflux scenario, is significantly impaired in patients with RE, whereas the rate of salivary PGE2 output remains essentially unchanged. Salivary secretory response to esophageal mechanical and chemical stimuli in terms of organic components, mediated by the esophagosalivary reflex pathway, exhibits a significant impairment in patients with reflux esophagitis.

Effects of sialoadenectomy and exogenous EGF on molar drift and orthodontic tooth movement in rats.

Effects on bone remodeling have been attributed to epidermal growth factor (EGF). Sialoadenectomy (SX) removes the major source of EGF in rodents and decreases both salivary and serum EGF levels. EGF effects on rat alveolar bone remodeling manifested by molar drift (MD) and orthodontic tooth movement (OTM) were examined using the following two approaches: 1) EGF depletion by SX and replacement by orally administered EGF (50 micrograms.animal-1.day-1); 2) sham rats supplemented with matching amounts of EGF. MD and OTM were measured using cephalometric radiographs; bone formation was measured histomorphometrically using tetracycline labeling. Normal MD was not detected after SX, and alveolar bone formation was significantly reduced both around the tooth and in nondental sites. Replacement EGF given to SX rats and supplemental EGF administered to sham rats changed the direction and enhanced the rate of MD. A mesially directed orthodontic force applied to the molars of SX animals increased bone formation on the distal aspect of the tooth roots. Supplemental EGF did not significantly affect OTM. EGF affects alveolar bone remodeling, as manifested clinically by alterations in normal maxillary MD.

Interaction of nitric oxide and salivary gland epidermal growth factor in the modulation of rat gastric mucosal integrity.

1. The interaction between endogenous nitric oxide (NO) and factors from the rat submandibular salivary gland such as epidermal growth factor (EGF) on gastric mucosal integrity in the rat has been investigated. 2. Bolus administration of the NO synthase inhibitor, NG nitro-L-arginine methyl ester (L-NAME; 6.25-50 mg kg-1, i.v.) to animals treated intraluminally with 0.15 N HCl resulted in a significant increase in the area of mucosal haemorrhagic damage at doses 12.5 and 50 mg kg-1. Concurrent administration of indomethacin (5 mg kg-1, i.v.) resulted in a significant haemorrhagic mucosal damage in response to L-NAME (12.5-50 mg kg-1). Administration of the highest dose of L-NAME resulted in an increase in histological damage to the rat gastric mucosa. 3. When compared to control animals, the extent of damage produced by L-NAME or L-NAME in combination with indomethacin was significantly exacerbated in rats which had been sialoadenectomized (SALX) by removal of the submandibular salivary glands. The mucosal damage in SALX rats was ameliorated by treatment with EGF (5 and 10 micrograms kg-1, i.v.). 4. L-NAME administration resulted in a small reduction of gastric mucosal blood flow as assessed by laser Doppler flowmetry (LDF). The reduction in LDF by 25 and 50 mg kg-1 L-NAME was significantly greater in SALX rats than in rats with intact salivary glands. Pretreatment of SALX rats with indomethacin did not augment this large decrease in LDF suggesting that endogenous prostanoids do not interact with NO and salivary factors in regulating mucosal microcirculation. 5. Mucosal NO biosynthesis as assessed by ['4C]-citrulline formation was reduced in SALX rats when compared to control animals. Pretreatment of SALX animals with parenterally-administered EGF(10 microg kg-1) was associated with an increase in [14C]-citrulline formation in the gastric mucosa to levels observed in control SALX rats.6. These data suggest that factors which originate from the salivary gland such as EGF interact with NO in the maintenance of mucosal integrity. The effects may be mediated at least in part by changes in gastric mucosal blood flow. Salivary glands and EGF may mediate these effects to some extent via changes in mucosal NO biosynthesis.

Increased rate of salivary epidermal growth factor secretion in patients with juvenile periodontitis

We compared salivary epidermal growth factor (EGF) concentrations in patients with juvenile periodontitis (JP) and periodontally healthy controls. In initial screening of 45 JP patients and a group of healthy controls, significantly higher salivary EGF concentrations were measured in the JP patients. Subsequently, 17 JP patients who had high EGF concentrations in some of their salivary samples were chosen, and a group of age- and sex-matched controls was selected. We then examined their EGF concentrations and EGF secretion rates under standardized conditions in stimulated and unstimulated saliva and studied the expression of EGF receptor (EGF-R) in their gingival tissues. The results showed that the mean EGF concentration (pmol/ml) was slightly higher in JP patients than in controls. However, the difference was statistically significant only in stimulated saliva and when calculated per milligram salivary protein. When EGF release was measured as the rate of EGF secretion (pg/min), significantly higher values were observed in JP patients than in controls both in unstimulated and stimulated saliva. Immunofluorescence microscopy (IF) of gingival samples from JP patients and their controls revealed no quantitative or qualitative differences in the expression of EGF-R. Our results demonstrate the complex nature of salivary EGF release. The elevated rate of salivary EGF secretion in JP patients may be associated with the pathogenetic mechanisms of juvenile periodontitis.

Effect of cigarette smoking on salivary epidermal growth factor (EGF) and EGF receptor in human buccal mucosa

The mouth acts as a primary target for cigarette smoke which is associated with several oral diseases and cancer. The present study investigated the effect of cigarette smoking on salivary EGF and the buccal EGF receptor. Samples of whole saliva and buccal biopsy were obtained from 15 healthy volunteers (10 smokers and 5 non-smokers). The smokers smoked 20 or more cigarettes/day for more than 5 years. Salivary cotinine (a major metabolite of nicotine) was determined by radioimmunoassay (RIA). The salivary cotinine level was consistent with the self-reported smoking status (smokers, 106–530 ng/ml saliva; non-smokers, <2 ng/ml saliva). As compared to the non-smokers, the salivary EGF concentration (determined by RIA) was 32% lower in those smokers whose salivary cotinine level was 250 ng/ml or higher (non-smokers, 2.21 ± 0.16; smokers, 1.57 ± 0.09 ng/ml saliva; mean ± S.E.M., P < 0.01). There was no significant difference in 125I-labeled EGF binding to the buccal receptor between the two groups. However, EGF stimulated the autophosphorylation of a 170-kDa protein band in the sample of non-smokers, but not in the smokers. The immunoblot analysis using anti-EGF receptor antibody indicated that the smoking-related deficiency in EGF receptor autophosphorylation was due to the functional alteration of the receptor proteins. In conclusion, cigarette smoking reduces the salivary EGF level and impairs the function of buccal EGF receptor, which may be associated with the pathology of smoking-related oral disease.

Depression of salivary epidermal growth factor by smoking.

Depression of salivary epidermal growth factor by smoking.

Safety of subaqua diving with a patent foramen ovale.

Comment Our data show that smoking is associated with reduced salivary secretion of epidermal growth factor and an increased prevalence of peptic ulc?ration in patients attending for endoscopy. Cigarette smoking could thus predispose to peptic ulcer by depressing salivary secretion of epidermal growth factor. Depression of submandibular epidermal growth factor concentration in a small group of patients with gastric and duodenal ulcers has been reported.4 Our data suggest that reductions in epidermal growth factor secretion in patients with ulcers are likely to be attributable to the higher proportion of patients with ulcers who are smokers. Smoking is associated with depressed prostaglandin synthesis, while nicotine can enhance platelet aggre? gation, vasoconstriction, and increased concentrations of circulating catecholamines.5 Carbon monoxide may depress oxygen transport.5 However, neither the mediator nor the mechanism by which smoking depresses production of salivary epidermal growth factor is clear. Epidermal growth factor is produced by Brunner's glands in the duodenum, as well as by a cell lineage which develops at the site of gastrointestinal ulc?ration. If smoking also depresses local mucosal synthesis or secretion of epidermal growth factor this might represent an additional factor predisposing to duodenal ulc?ration as well as a plausible explana? tion for the link between smoking and Crohn's disease.

唾液腺の上皮成長因子（ＥＧＦ）に関する研究 ヒト唾液腺組織のＥＧＦとＥＧＦ受容体

Epidermal growth factor (EGF) stimulates the growth and differentiation of normal and tumor tissues after binding to its receptor (EGFR). To study the correlation between histological malignancy of salivary gland tumors and expression of EGFR or EGF, we investigated immunohistochemical expressions of EGFR and EGF in normal salivary glands and salivary gland tumors (n=136).In normal salivary glands (parotid, submaxillary, sublingual and minor salivary glands), EGFR and EGF were detected in ductal segments of intercalated, striated, and excretory ducts, but not in acinar cells. In salivary gland tumors, EGFR and EGF were positive in luminal tumor cells and squamous metaplastic cells in pleomorphic adenoma, tumor cells in adenolymphoma, epidermoid tumor cells in mucoepidermoid tumor, luminal tumor cells of tubular pattern in adenoid cystic carcinoma, and all tumor cells in adenocarcinoma and epidermoid carcinoma. But they were negative in acinic cell tumor, mucous tumor cells in mucoepidermoid tumor, tumor cells of cribriform pattern and outer tumor cells of tubular pattern in adenoid cystic carcinoma.EGFR and EGF are positive in duct-like arrangement cells of pleomorphic adenoma and adenolymphoma, which are considered to be well differentiated. On the other hand EGFR and EGF positive cells the arrangement of which is not similar to duct structures like adenocarcinoma or epidermoid carcinoma are thought to have more potential for growth. The EGFR positive rate is 100% in adenocarcinoma and epidermoid carcinoma which have a poor prognosis. The synchronous expression of EGFR and EGF may play some biological role in tumor proliferation by an autocrine mechanism.

The Interrelationship Between Salivary Epidermal Growth Factor and the Functional Integrity of the Esophageal Mucosal Barrier in the Rat

The role of salivary epidermal growth factor (sEGF) in the maintenance of the esophageal mucosal mucus coat and its permselective properties was investigated for this study. Eighteen Sprague-Dawley male rats underwent sialoadenectomy (SAD), while 18 others with sham operation served as a control. Nine SAD rats in each group received EGF in a dose of 15 micrograms/kg/d for five consecutive days prior to sacrifice. Esophageal mucosa dissected from the muscle layer was placed in the central port of a specially designed permeability chamber filled on both sides with equimolar solutions of NaCl or HCl (0.155 M). The rate of hydrogen ion diffusion from the mucosal to the serosal side was estimated by continuous recording of pH in the NaCl compartment. In addition, the mucosal mucus coat was evaluated by Alcian blue uptake methodology. SAD led to a 108% increase in the rate of permeability of the esophageal mucosa to hydrogen ion. Simultaneously, an 83% decrease in the mucus content on the surface of the esophageal mucosa was observed. A five-day supplementation of EGF substantially improved the permeability of esophageal mucosa (67%) and the mucous layer of esophagus (41%). sEGF seems to play an important physiological role in the maintenance of the functional integrity of the esophageal mucosa.

Increased Salivary Concentration of Human Epidermal Growth Factor in Patients Undergoing CAPD

Epidermal growth factor (EGF) was measured in the saliva of 36 patients with chronic renal failure (CRF) and 29 matched control subjects. Salivary EGF in controls was 0.65 +/- 0.009 nmol/L compared with 0.99 +/- 0.24 nmol/L in nondialyzed CRF patients, 1.15 +/- 0.23 in hemodialyzed patients and 1.96 +/- 0.25 (p less than 0.01, Wilcoxon Rank Sum Test) in CAPD-treated patients. On Sephadex chromatography, the major peak of immunoreactive EGF from patient and control saliva samples coeluted with purified human EGF. We conclude that salivary concentrations of human EGF are significantly elevated in end-stage renal failure, particularly in patients treated by CAPD.

Physiologic levels of salivary epidermal growth factor stimulate migration of an oral epithelial cell line

An established line of human oral epithelial cells exhibits chemotaxis to epidermal growth factor (EGF). The directed migration of these cells is time dependent with an approximate 10-fold increase in the number of cells responding to the chemoattractant by 6 h. Cell migration occurs in a concentration dependent manner with maximal response at ≈ 1 ng/ml. This maximal chemotactic response occurs within the physiologic concentration range for EGF found in human saliva. These data suggest that EGF may be important for the maintenance of an intact oral epithelial (mucosal) barrier, and may play a vital role in oral mucosal wound healing.

Effect of salivary epidermal growth factor on wound healing of tongue in mice

The role of salivary epidermal growth factor (EGF) in wound healing of the tongue was studied in mice. Sialoadenectomy (removal of the submandibular glands, which are the major source of salivary EGF) or sham operation was performed 2 wk before infliction of wound on the tongue. Salivary EGF levels were 1.98 +/- 0.47 and 0.20 +/- 0.04 (SE) microgram/ml in sham-operated male and female mice, respectively, whereas sialoadenectomy reduced salivary EGF to undetectable levels in both male and female mice. A circular superficial wound measuring approximately 2 mm in diameter was made in the middle of the tongue by mechanically ablating only the epithelial layer. The rate of wound healing was monitored by a stereomicroscopy. Sialoadenectomized male mice showed a significant delay in wound healing compared with sham-operated controls. Treatment of sialoadenectomized male mice with EGF (1 microgram/ml in drinking water) restored the rate of wound healing to normal levels. Transforming growth factor (1 microgram/ml) was as effective as EGF in the promotion of wound healing, whereas nerve growth factor (1 microgram/ml) was ineffective. Essentially the same results were obtained in female mice. In addition, two classes of EGF binding sites with high and low affinity were demonstrated in the epithelium of the tongue obtained from male and female mice. The maximum binding sites and dissociation constants of the EGF receptors were the same between males and females and were not affected by sialoadenectomy. These results suggest that salivary EGF is involved in the promotion of wound healing of the tongue in both male and female mice.

Lack of effects of viral sialoadenitis and depletion of epidermal growth factor on initiation of hepatic carcinogenesis in the rat.

Sialodacryoadenitis (SDA) is a commonly-encountered coronaviral infection in laboratory rats that causes acute destruction of submandibular salivary glands. SDA results in depletion of salivary epidermal growth factor (EGF) and may thereby affect EGF-dependent cell growth processes. The purpose of this study was to determine the effects of SDA virus (SDAV) infection on the growth factor-dependent stages of experimental liver carcinogenesis. Rats were injected ip with the carcinogen diethylnitrosamine (DENA) at 1, 2, or 3 weeks following inoculation with SDAV. Uninfected control rats were treated only with DENA. The salivary glands of SDAV-inoculated and control rats were stained using the immunoperoxidase method for the detection of EGF. Residual submandibular salivary gland lesions and focal depletion of EGF were still evident in affected submandibular glands for up to 42 days after SDAV infection. Serum EGF concentrations measured at 9, 28, and 42 days following SDAV inoculation were reduced, but were not significantly different in comparison with non-inoculated, DENA-treated control rats. Initiated hepatocytes were detected 21 days after DENA treatment in formalin-fixed sections by an immunoperoxidase stain for the P isoenzyme of the enzyme glutathione S-transferase (GST-P). There was no significant difference in the number of foci of GST-P positive cells in a comparison of initiated cells in SDAV-inoculated and non-inoculated rats. Based on this model, concurrent infection with SDAV does not appear to have any significant effects on the initial stages of chemical hepatocarcinogenesis in the rat.

Salivary epidermal growth factor in patients with peptic ulcer

Salivary epidermal growth factor in patients with peptic ulcer

Decreased salivary epidermal growth factor in rheumatoid disease.

Decreased salivary epidermal growth factor in rheumatoid disease.

Decreased salivary epidermal growth factor in rheumatoid disease

Decreased salivary epidermal growth factor in rheumatoid disease

Secretion of epidermal growth factor in parotid saliva in diabetic patients: role of autonomic innervation

Parotid saliva was collected over a 12-min period from 24 insulin dependent diabetic patients with varying degrees of autonomic neuropathy and 12 age and sex matched non-diabetic controls. Epidermal growth factor (EGF) concentrations in saliva were measured by radio-immunoassay. The EGF concentrations in diabetics with no autonomic neuropathy or with combined autonomic neuropathy were equivalent but secretion of EGF was significantly elevated at the 6- and 12-min periods of collection in diabetic patients with early or established autonomic neuropathy. It is postulated that when parasympathetic autonomic neuropathy is present a relative "over-activity" of the sympathetic innervation promotes release of salivary EGF. This sympathetic predominance may maintain salivary EGF concentration despite the elevated salivary flow and volume which is associated with parasympathetic autonomic neuropathy.

Decreased salivary epidermal growth factor in rheumatoid disease: a possible mechanism for increased susceptibility to gastric ulceration.

Decreased salivary epidermal growth factor in rheumatoid disease: a possible mechanism for increased susceptibility to gastric ulceration.

Saliva from cystic fibrosis patients contains an unusual form of epidermal growth factor

Epidermal Growth Factor (EGF) was assayed in saliva collected from control subjects and cystic fibrosis (CF) patients, using both radioimmuno (RIA) and radioreceptor (RRA) assays. An intriguing finding was that the average ratio of the values found by RRA over those obtained by RIA was of 1.7 for normal subjects and of about 0.4 for CF patients. This observation could be understood following gel filtration analysis of EGF-like material in these salivary fluids. Whereas control saliva contained the expected 6 kDa EGF active peptide, the immunoreactive EGF material from CF patients eluted as a polydisperse macromolecular moiety. The poor biological reactivity of this material as assessed by radioreceptor assay suggests that this EGF anomaly may contribute to the physiopathology of cystic fibrosis, especially as the upper gastrointestinal tract differentiated functions may be the target of normal salivary EGF.