Increased production of transforming growth factor α following acute gastric injury

doi:10.1016/0016-5085(92)91703-7

Gastroenterology

Volume 102, Issue 5, May 1992, Pages 1467-1474

https://doi.org/10.1016/0016-5085(92)91703-7 Get rights and content

Abstract

Transforming growth factor a (TGF-α) production recently has been found in normal mammalian gastric mucosa. Inasmuch as TGF-α and epidermal growth factor (EGF) both stimulate epithelial cell migration and proliferation and suppress gastric acid secretion, the authors of the current study proposed that these growth factors may participate in tissue repair after acute gastric mucosal injury. Consequently, TGF-α and EGF production were examined after orogastric administration of either acidified taurocholate or 0.6 mol/L HCl to rats. TGF-α messenger RNA (mRNA) expression increased in a dose- and time-dependent manner after administration of taurocholate, whereas EGF mRNA expression was not detected. Radioimmunoassay of gastric mucosal scrapings obtained 6 hours after gastric injury induced by 0.6 mol/L HCl showed a 2.1-fold increase in immunoreactive TGF-α but no increase in immunoreactive EGF. In addition, there was a 68-fold increase in immunoreactive TGF-α in gastric juice within 30 minutes of gastric instillation of HCl and, again, no increase in immunoreactive EGF. There is a rapid appearance of TGF-α in the gastric juice within 30 minutes of injury, which is followed by increased expression of TGF-α mRNA and protein in the gastric mucosa. These studies suggest that locally produced TGF-α may participate in gastric mucosal repair following acute gastric injury to rats.

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No publications were found that assessed the salivary concentrations of TGF-α and their possible involvement in the genesis of supraesophageal manifestations of GERD. However, when analyzing the few studies on the participation of this growth factor in the homeostasis of the digestive system, the results observed in this analysis agree with those published by Polk et al., who reported an increase in the production of TGF-α in response to acute gastric aggression with HCl.50 Similar finding was observed by Fujiwara et al., when analyzing mice with chronic reflux esophagitis.15
Saliva plays a key role in the homeostasis of the digestive tract, through its inorganic components and its protein growth factors. Sjögren's syndrome patients have a higher prevalence of gastroesophageal reflux disease and laryngopharyngeal reflux. Decreased salivary transforming growth factor alpha levels were observed in dyspeptic patients, but there have been no studies in patients with Sjögren's syndrome and laryngopharyngeal reflux.
To compare the salivary transforming growth factor alpha levels of patients with Sjögren's syndrome and laryngopharyngeal reflux to those of healthy controls.
This is a prospective controlled study. Twelve patients with Sjögren's syndrome and laryngopharyngeal reflux and 11 controls were prospectively evaluated. Spontaneous and stimulated saliva samples were obtained to establish salivary transforming growth factor alpha concentrations.
The salivary transforming growth factor alpha levels of patients were significantly higher than those of healthy controls. Five patients with laryngopharyngeal reflux also had erosive esophagitis; their salivary transforming growth factor alpha levels were comparable to controls.
Salivary transforming growth factor alpha level was significantly higher in patients with Sjögren's syndrome and laryngopharyngeal reflux when compared to the control group.
A saliva exerce influência primordial na homeostase do sistema digestório, pelos seus componentes inorgânicos e pelos fatores de crescimento. Indivíduos com síndrome de Sjögren (SS) apresentam maior incidência da doença do refluxo gastroesofágico (DRGE) e do refluxo laringofaríngeo (RLF). Concentrações salivares diminuídas do fator transformador de crescimento-alfa (TGF-α) foram observadas em doentes dispépticos, porém não há estudos em populações com SS e RLF.
Comparar concentrações salivares do TGF-α; de indivíduos com SS e RLF a de controles saudáveis.
Trata-se de um estudo prospectivo controlado. Doze pacientes com SS e RLF e 11 indivíduos controles saudáveis tiveram amostras salivares espontâneas e estimuladas coletadas para estabelecer concentração de TGF-α.
A concentração salivar de TGF-α; foi estatisticamente maior no grupo estudo para ambas amostras. Este aumento foi confirmado nos sete indivíduos do grupo estudo que não apresentavam esofagite erosiva quando comparados ao grupo controle, porém não houve diferença estatística da concentração de TGF-α; entre pacientes do grupo estudo que apresentavam esofagite erosiva em comparação ao grupo controle.
A concentração salivar de TGF-α; foi estatisticamente maior no grupo de indivíduos com SS e RLF, sem esofagite erosiva.
Substance P and calcitonin gene related peptide induce TGF-alpha expression in epithelial cells via mast cells and fibroblasts
2010, Regulatory Peptides
Signals for the expression of EGF, TGFα and related proteins are largely unknown. Having shown earlier, that activation of the afferent sensory nervous system by capsaicin induced epithelial cell proliferation and TGFα expression in vivo the aim of this study was to demonstrate, that neurotransmitters of the afferent sensory nervous system induce TGFα expression via mast cells and fibroblasts.
A significant increase in TGFα-mRNA and protein expression was detected in epithelial cells exposed to supernatants of CGRP-stimulated mast cells and SP-stimulated fibroblasts. Epithelial cell proliferation was only detected in epithelial cells exposed to supernatants of CGRP-stimulated mast cells but not in epithelial cells exposed to supernatants of SP-stimulated fibroblasts. TGFβ mRNA expression was increased in epithelial cells exposed to fibroblasts but not to mast cells. No increase in EGF-receptor expression was detected in epithelial cells exposed to either fibroblast or mast cell supernatants.
Neurotransmitters of the afferent sensory nervous system induce TGFα expression in epithelial cells mediated by mast cells and fibroblasts. Release of CGRP and SP from neuroeffector junctions is an important signal for the TGFα expression after mucosal injury. Mucosal expression of TGFα may contribute to the protective effects of the sensory nervous system after mucosal injury.
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The aim of the present study is to investigate the antiulcerogenic effects of the essential oil (EO) of Croton cajucara Benth in rats fed with a normal protein (NP) and low-protein diet (MN).
NP and MN rats were treated with the essential oil for 15 days after chronic ulceration was induced. The EO accelerated healing of acetic acid-induced gastric lesions in NP and MN rats (p<0.05). In a similar experiment on chronic ulceration, Epidermal Growth Factor (EGF) mRNA expression increased in NP rats but not in MN rats.
In assays of acute antiulcerogenic activity, C. cajucara increased somatostatin plasma levels and decreased gastrin plasma levels in both animal groups. The EO significantly prevented ethanol-induced gastric ulcers in NP and MN rats (p<0.001).
Histological examination showed initial regeneration, formation of inflammatory infiltrate and angiogenesis in the epithelium surface of acetic acid-induced ulcers in NP and MN rats. C. cajucara prevented gastric lesions in both animal groups when ethanol methodology was used. We concluded that the EO showed an antiulcerogenic activity mediated by increased somatostatin secretion and EGF mRNA expression.
Gastrin and interleukin-1β stimulate growth factor secretion from cultured rabbit gastric parietal cells
2004, Life Sciences
The hormone gastrin stimulates proliferation of the gastric mucosa. Inflammation of the stomach is also associated with increased proliferation. The proliferative response is important in the reparative response to injury but can be deleterious by predisposing to the development of cancer. Parietal cells, but not the cells in the proliferative zone of the gastric glands, express the appropriate gastrin receptor. Parietal cells may mediate the trophic effects of gastrin by secreting other growth factors. The role of parietal cells in the proliferative responses has been examined in this study. Rabbit parietal cells were cultured with gastrin or the cytokine interleukin-1β for 18 hours. The conditioned medium from gastrin or IL-1β stimulated parietal cells increased proliferation of HeLa cells in an epidermal growth factor-receptor dependant manner. Gastrin and IL-1β stimulated the secretion of heparin-binding epidermal growth factor and amphiregulin but not transforming growth factor-α from parietal cells. Combinations of gastrin and IL-1β on growth factor secretion were synergistic. The protein kinase C inhibitor staurosporine abolished these stimulatory effects of gastrin and IL-1β. Divergent effects on histamine-stimulated acid secretion were observed; 18 hours pre-treatment with gastrin enhanced acid secretion by 50% but IL-1β inhibited acid secretion in both control and gastrin pre-treated parietal cells.
The acid-secreting parietal cell plays a central role in the regulation of mucosal proliferation in gastric inflammation. Secretion of paracrine growth factors by parietal cells may be an important point of integration between the endocrine and inflammatory stimuli in determining mucosal responses to injury and inflammation.
Long-term outcomes of radical surgery after gasless video endoscopic transanal excision of T1/T2 rectal cancers
2004, European Journal of Surgical Oncology
Citation Excerpt :
The current study revealed favorable long-term oncological outcomes after additional radical surgery following gasless VTEM in patients with high-risk T1 and T2 carcinomas. Growth factors play important roles not only in tumour growth but also in wound healing.9,24 Endoscopic snare polypectomy makes a large open wound in gastrointestinal mucosa and stimulates the wound-healing mechanism.
Aims. We aim to clarify the long-term outcomes after an additional radical operation following gasless video endoscopic transanal rectal tumour excision (gasless VTEM) of ‘high-risk’ T1 and T2 rectal cancer.
Methods. Gasless VTEM involves modification of transanal endoscopic microsurgery (TEM) by incorporating a standard laparoscopic video camera without a CO₂ insufflation system. This study between 1993 and 2003 included six men and five women with a median age of 64 years (range, 36–79). Specimens resected by gasless VTEM revealed (1) high-risk T1 carcinomas with one of the following histological types: poorly differentiated, lymphovascular invasion, and massive invasion of the submucosa (submucosal invasion greater than 200–300 μm from the muscularis mucosa) and (2) T2 carcinomas.
Results. Eight patients had a high-risk T1 carcinoma and three patients had a T2 carcinoma. In two patients with a high-risk T1 carcinoma, a residual tumour was found in the specimen resected by the additional radical surgery. At a median follow-up of 86.5 months (range, 63.2–110.5), none of the patients developed tumour recurrence. Although one patient died with cancer at another organ site (hilar cholangiocarcinoma of the liver) 87 months after the additional radical surgery, the other 10 patients are alive and disease free.
Conclusions. This study revealed favorable long-term outcomes after additional radical surgery following gasless VTEM in patients with high-risk T1 and T2 carcinomas.
Functional interaction between transforming growth factor α and capsaicin-sensitive sensory neurons in the rat stomach
2004, Regulatory Peptides
Background and aims: Transforming growth alpha (TGFα) and sensory neurons have been shown to promote gastric mucosal protection and healing. Aims were to examine in vitro interactions between gastric sensory neurons, the sensory neuropeptide calcitonin gene-related peptide (CGRP), and TGFα. Methods: Gastric mucosal/submucosal tissue fragments from Sprague–Dawley (SD) rats were incubated in short-term (30 min) culture. Peptide release into media and TGFα tissue content were measured by radioimmunoassay. Results: TGFα (1×10⁻⁸ to 1×10⁻⁶ M) caused dose-dependent stimulation of CGRP release. Maximal CGRP release (+87%) was observed with 1×10⁻⁶ M TGFα: 28.6±3.8 vs. control of 15.5±2.7 pg/g tissue; P<0.05. Both CGRP (1×10⁻⁷ to 1×10⁻⁵ M) and capsaicin (1×10−⁸ to 1×10⁻⁶M) significantly inhibited basal TGFα release in a dose-dependent fashion that ranged from −20% to −39%. In contrast, capsaicin-induced sensory denervation caused significant increases in both basal TGFα release and TGFα tissue content. Conclusion: Function interactions between TGFα and gastric sensory neurons are suggested by the observations that (1) TGFα stimulated CGRP release from gastric sensory neurons; (2) CGRP and acute capsaicin treatment inhibited TGFα release and; (3) capsaicin-induced sensory denervation caused significant increases in both gastric TGFα basal release and tissue content.

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²: Supported by NCI CA 08815-02 (W.H.P.).

⁴: Supported by NCI DK 44557 (W.E.R.).

³: Supported by NCI CA 01309 (R.D.B.).

¹: Supported by National Cancer Institute (NCI) CA 46413; Veterans Administration and Culpeper Foundation (R.J.C.).

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Increased production of transforming growth factor α following acute gastric injury

Abstract

Gastroenterology

Gastroenterology

Gastroenterology

Gastroenterology

Gastroenterology

Regul Pep

Biochem Biophys Res Comm

Biochem Biophys Acta

Gastroenterology

Cell

Cell

Methods Enzymol

Cell

Cell

Cell

Cell

J Biol Chem

Requirements for restitution of the surface epithelium of frog stomach after mucosal injury

Gastroenterology

Electron microscopic study of the repair of aspirin-induced gastric erosions

Am J Dig Dis

Regeneration of gastric mucosa after aspirin-induced injury in the rat

Dig Dis Sci

Basal lamina scaffold: anatomy and significance of orderly tissue structure. A review

Am J Pathol

Epidermal growth factor promotes the chemotactic migration of cultured rat intestinal epithelial cells

J Cell Physiol

Proliferative effects of urogastrone-EGF on the intestinal epithelium

Gut

Stimulation of rat oxyntic gland mucosal growth by epidermal growth factor

Am J Physiol