Diminished salivary epidermal growth factor secretion: a link between Sjögren’s syndrome and autoimmune gastritis?

Koskenpato, Katja; Ainola, Mari; Przybyla, Beata; Vp, Kouri; L, Virkki; Koskenpato, Jari; Ristimäki, Ari; Yt, Konttinen

doi:10.3109/03009742.2015.1072243

Cited by 7 publications

(6 citation statements)

References 14 publications

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“…After binding to the EGF receptor it regulates epithelial cell proliferation and survival and therefore is thought to have protective effects. EGF has previously been shown to be reduced in tears (67), salivary glands (68, 69) and saliva of pSS patients and correlates with progression of intraoral manifestations (70, 71). FTCD is a metabolic enzyme, which is primary active in the liver and kidneys.…”

Section: Discussionmentioning

confidence: 97%

Fatigue in Sjögren's Syndrome: A Search for Biomarkers and Treatment Targets

et al. 2019

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Background: Primary Sjögren's syndrome (pSS) is a systemic autoimmune disease, where patients often suffer from fatigue. Biological pathways underlying fatigue are unknown. In this study aptamer-based SOMAscan technology is used to identify potential biomarkers and treatment targets for fatigue in pSS. Methods: SOMAscan® Assay 1.3k was performed on serum samples of healthy controls (HCs) and pSS patients characterized for interferon upregulation and fatigue. Differentially expressed proteins (DEPs) between pSS patients and HC or fatigued and non-fatigued pSS patients were validated and discriminatory capacity of markers was tested using independent technology. Results: Serum concentrations of over 1,300 proteins were compared between 63 pSS patients and 20 HCs resulting in 58 upregulated and 46 downregulated proteins. Additionally, serum concentrations of 30 interferon positive (IFNpos) and 30 interferon negative (IFNneg) pSS patients were compared resulting in 25 upregulated and 13 downregulated proteins. ELISAs were performed for several DEPs between pSS patients and HCs or IFNpos and IFNneg all showing a good correlation between protein levels measured by ELISA and relative fluorescence units (RFU) measured by the SOMAscan. Comparing 22 fatigued and 23 non-fatigued pSS patients, 16 serum proteins were differentially expressed, of which 14 were upregulated and 2 were downregulated. Top upregulated DEPs included neuroactive synaptosomal-associated protein 25 (SNAP-25), alpha-enolase (ENO1) and ubiquitin carboxyl-terminal hydrolase isozyme L1 (UCHL1). Furthermore, the proinflammatory mediator IL36a and several complement factors were upregulated in fatigued compared to non-fatigued pSS patients. ROC analysis indicated that DEPs showed good capacity to discriminate fatigued and non-fatigued pSS patients. Conclusion: In this study we validated the use of aptamer-based proteomics and identified a novel set of proteins which were able to distinguish fatigued from non-fatigued pSS patients and identified a so-called “fatigue signature.”

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Section: Discussionmentioning

confidence: 97%

Fatigue in Sjögren's Syndrome: A Search for Biomarkers and Treatment Targets

et al. 2019

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“…Transforming growth factor-α (TGF-α) is expressed throughout the gastrointestinal tract and is abundant in parietal cells ( 30 ). Epidermal growth factor (EGF) is secreted into salivary fluid ( 207 ), although whether breaches in the lumen can lead to access to basolateral EGF receptors in physiological conditions remains unclear. TGF-α and EGF share amino acid homology and a common receptor, namely, ErbB (EGFR), which is predominantly expressed on the basolateral membranes of parietal cells and is weakly detected in mucous neck cells and chief cells in healthy humans ( 3 ).…”

Section: Regulation Of Gastric Acid Secretionmentioning

confidence: 99%

The Physiology of the Gastric Parietal Cell

Engevik

Kaji

Goldenring

2020

Physiological Reviews

170

103

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Parietal cells are responsible for gastric acid secretion, which aids in the digestion of food, absorption of minerals, and control of harmful bacteria. However, a fine balance of activators and inhibitors of parietal cell-mediated acid secretion is required to ensure proper digestion of food, while preventing damage to the gastric and duodenal mucosa. As a result, parietal cell secretion is highly regulated through numerous mechanisms including the vagus nerve, gastrin, histamine, ghrelin, somatostatin, glucagon-like peptide 1, and other agonists and antagonists. The tight regulation of parietal cells ensures the proper secretion of HCl. The H+-K+-ATPase enzyme expressed in parietal cells regulates the exchange of cytoplasmic H+ for extracellular K+. The H+ secreted into the gastric lumen by the H+-K+-ATPase combines with luminal Cl− to form gastric acid, HCl. Inhibition of the H+-K+-ATPase is the most efficacious method of preventing harmful gastric acid secretion. Proton pump inhibitors and potassium competitive acid blockers are widely used therapeutically to inhibit acid secretion. Stimulated delivery of the H+-K+-ATPase to the parietal cell apical surface requires the fusion of intracellular tubulovesicles with the overlying secretory canaliculus, a process that represents the most prominent example of apical membrane recycling. In addition to their unique ability to secrete gastric acid, parietal cells also play an important role in gastric mucosal homeostasis through the secretion of multiple growth factor molecules. The gastric parietal cell therefore plays multiple roles in gastric secretion and protection as well as coordination of physiological repair.

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“…The interplay between the gut microbiota, the epithelium and the immune cells of the gastrointestinal mucosa has been shown to have significant effects on the local and systemic immune systems [11] and may both decrease and increase local and systemic inflammatory disease [12]. In pSS patients, it has been considered that, the integrity of the gastrointestinal epithelium and its barrier function may be altered through inflammation and diminished secretions of the exocrine glands, producing an altered microbiota-host immune system interaction [13,14]. Exocrine gland dysfunction is driven by high levels of key factors such as proinflammatory cytokines including interleukin (IL)-12, IL-6, interferon-gamma (IFN-gamma) and tumor necrosis factor (TNF)-alpha; serum autoantibodies including antinuclear antibodies (ANA), antibodies against anti-Ro/Sjögren's syndrome autoantibody A (Ro/SSA) and anti La/Sjögren's syndrome autoantibody B (La/SSB), and rheumatoid factor (RF); and significant infiltration of T and B cells [15].…”

Section: Introductionmentioning

confidence: 99%

Connection between the Gut Microbiome, Systemic Inflammation, Gut Permeability and FOXP3 Expression in Patients with Primary Sjögren’s Syndrome

Cano-Ortiz

Laborda-Illanes

Plaza-Andrades

et al. 2020

IJMS

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The aims of this study were to explore intestinal microbial composition and functionality in primary Sjögren’s syndrome (pSS) and to relate these findings to inflammation, permeability and the transcription factor Forkhead box protein P3 (FOXP3) gene expression in peripheral blood. The study included 19 pSS patients and 19 healthy controls matched for age, sex, and body mass index. Fecal bacterial DNA was extracted and analyzed by 16S rRNA sequencing using an Ion S5 platform followed by a bioinformatics analysis using Quantitative Insights into Microbial Ecology (QIIME II) and Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt). Our data suggest that the gut microbiota of pSS patients differs at both the taxonomic and functional levels with respect to healthy controls. The gut microbiota profile of our pSS patients was characterized by a lower diversity and richness and with Bacteroidetes dominating at the phylum level. The pSS patients had less beneficial or commensal butyrate-producing bacteria and a higher proportion of opportunistic pathogens with proinflammatory activity, which may impair intestinal barrier function and therefore contribute to inflammatory processes associated with pSS by increasing the production of proinflammatory cytokines and decreasing the release of the anti-inflammatory cytokine IL-10 and the peripheral FOXP3 mRNA expression, implicated in the development and function of regulatory T cells (Treg) cells. Further studies are needed to better understand the real impact of dysbiosis on the course of pSS and to conceive preventive or therapeutic strategies to counteract microbiome-driven inflammation.

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Diminished salivary epidermal growth factor secretion: a link between Sjögren’s syndrome and autoimmune gastritis?

Cited by 7 publications

References 14 publications

Fatigue in Sjögren's Syndrome: A Search for Biomarkers and Treatment Targets

Fatigue in Sjögren's Syndrome: A Search for Biomarkers and Treatment Targets

The Physiology of the Gastric Parietal Cell

Connection between the Gut Microbiome, Systemic Inflammation, Gut Permeability and FOXP3 Expression in Patients with Primary Sjögren’s Syndrome

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