Interleukin-Mediated Pendrin Transcriptional Regulation in Airway and Esophageal Epithelia

Vanoni, Simone; Scantamburlo, Giada; Dossena, Silvia; Paulmichl, Markus; Nofziger, Charity

doi:10.3390/ijms20030731

Cited by 8 publications

(11 citation statements)

References 172 publications

(223 reference statements)

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“…premature stop codon mutations), activation of TMEM16A could also restore Cl − /HCO 3 − efflux. As CFTR may regulate other channels and transporters like the epithelial Na + channel or pendrin in surface epithelial cells [36,40,41], TMEM16A activation may not fully replace CFTR. However, this study and previous work [6] suggest TMEM16A can support levels of Cl − and HCO 3 − efflux from serous cells equivalent to CFTR.…”

Section: Discussionmentioning

confidence: 99%

“…Type 2 inflammation was suggested to upregulate Cl − /HCO 3 − exchanger pendrin in airway surface epithelial cells [40,41]. We examined if NPY or IL-13 induced altered expression of pendrin or Cl − channels in primary serous cells, perhaps shifting serous cells away from CFTR toward a more TMEM16A-and/or pendrin-dominated secretory phenotype.…”

Section: Npy and Vip Have Opposing Effects On CL − And Hcomentioning

confidence: 99%

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Neuropeptide regulation of secretion and inflammation in human airway gland serous cells

et al. 2020

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Airway submucosal gland serous cells are sites of expression of the cystic fibrosis transmembrane conductance regulator (CFTR) and are important for fluid secretion in conducting airways. To elucidate how neuropeptides regulate serous cells, we tested if human nasal turbinate serous cells secrete bicarbonate (HCO3−), important for mucus polymerisation and antimicrobial peptide function, during stimulation with cAMP-elevating vasoactive intestinal peptide (VIP) and if this requires CFTR. Serous cells stimulated with VIP exhibited a ∼15–20% cAMP-dependent decrease in cell volume and a ∼0.15 unit decrease in intracellular pH (pHi), reflecting activation of Cl− and HCO3− secretion, respectively. HCO3− secretion was directly dependent on CFTR and was absent in cells from CF patients. In contrast, neuropeptide Y (NPY) reduced VIP-evoked cAMP increases, CFTR activation, and Cl−/HCO3− secretion. Culture of primary serous cells in a model that maintained a serous phenotype confirmed the activating and inhibiting effects of VIP and NPY, respectively, on fluid and HCO3− secretion. Moreover, VIP enhanced antimicrobial peptide secretion and antimicrobial efficacy of secretions while NPY reduced antimicrobial efficacy. In contrast, NPY enhanced cytokine release while VIP reduced cytokine release through a mechanism requiring CFTR. As levels of VIP and NPY are up-regulated in diseases like allergy, asthma, and chronic rhinosinusitis, the balance of these two peptides in the airway may control mucus rheology and inflammatory responses in serous cells. Furthermore, the loss of CFTR conductance in serous cells may contribute to CF pathophysiology by increasing serous cells inflammatory responses in addition to directly impairing Cl− and HCO3− secretion.

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Section: Discussionmentioning

confidence: 99%

Section: Npy and Vip Have Opposing Effects On CL − And Hcomentioning

confidence: 99%

Neuropeptide regulation of secretion and inflammation in human airway gland serous cells

et al. 2020

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“…Our results showed that IL‐11 could potentially be used as an independent prognostic factor for EAC. Among the interleukin family, secretion of IL‐33 in esophageal epithelial cells has been reported to prompt the occurrence of gastroesophageal reflux diseases and lead to Barrett esophagus; 31 IL‐4, IL‐13, 32 IL‐1β 33 and IL‐6 34 contributed to increased secretion of esophageal mucosa in patients with Barrett's esophagus, and IL‐11 contributed to esophageal squamous cell carcinoma progression and its aggressiveness 35 . Nonetheless, to date, no study has reported the role of IL‐11 in EAC, and our study fills this gap and confirms the potentially important role of it in EAC prognosis.…”

Section: Discussionmentioning

confidence: 99%

Multivariate gene expression‐based survival predictor model in esophageal adenocarcinoma

et al. 2020

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Background: Despite the recent development of molecular-targeted treatment and immunotherapy, survival of patients with esophageal adenocarcinoma (EAC) with poor prognosis is still poor due to lack of an effective biomarker. In this study, we aimed to explore the ceRNA and construct a multivariate gene expression predictor model using data from The Cancer Genome Atlas (TCGA) to predict the prognosis of EAC patients. Methods: We conducted differential expression analysis using mRNA, miRNA and lncRNA transciptome data from EAC and normal patients as well as corresponding clinical information from TCGA database, and gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of those unique differentially expressed mRNAs using the Integrate Discovery Database (DAVID) database. We then constructed the lncRNA-miRNA-mRNA competing endogenous RNA (ceRNA) network of EAC and used Cox proportional hazard analysis to generate a multivariate gene expression predictor model. We finally performed survival analysis to determine the effect of differentially expressed mRNA on patients' overall survival and discover the hub gene. Results: We identified a total of 488 lncRNAs, 33 miRNAs, and 1207 mRNAs with differentially expressed profiles. Cox proportional hazard analysis and survival analysis using the ceRNA network revealed four genes (IL-11, PDGFD, NPTX1, ITPR1) as potential biomarkers of EAC prognosis in our predictor model, and IL-11 was identified as an independent prognostic factor. Conclusions: In conclusion, we identified differences in the ceRNA regulatory networks and constructed a four-gene expression-based survival predictor model, which could be referential for future clinical research.

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“…The downregulation of secreted mucins could result from the ability of CSs to reduce GCH and could account for the reduction of mucus production and rhinorrhea [59]. The histological features of sinus mucosal lesions in CRS are the large number of inflammatory cell infiltration and cytokine release [60], particularly neutrophils [52,61,62], which were reported to be associated with mucosal remodeling. Sampson et al [63] showed that neutrophils played a role in remodeling by secreting recombinant mediators (such as MMPs and TGF-β) [64].…”

Section: Regulation Of Mucins In Crsmentioning

confidence: 99%

Expression and Clinical Significance of Mucin Gene in Chronic Rhinosinusitis

Tong

2020

Curr Allergy Asthma Rep

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Purpose of Review This review highlights the expression and regulation of mucin in CRS and discusses its clinical implications. Recent Findings Chronic rhinosinusitis (CRS) is common chronic nasal disease; one of its main manifestations and important features is mucus overproduction. Mucin is the major component of mucus and plays a critical role in the pathophysiological changes in CRS. The phenotype of CRS affects the expression of various mucins, especially in nasal polyps (NP). Corticosteroids(CS), human neutrophil elastase (HNE), and transforming growth factor-β1 (TGF-β1) are closely related to the tissue remodeling of CRS and regulate mucin expression, mainly MUC1, MUC4, MUC5AC, and MUC5B. “It is expected that CS, HNE and TGF - β could be used to regulate the expression of mucin in CRS.” However, at present, the research on mucin is mainly focused on mucin 5AC and mucin 5B, which is bad for finding new therapeutic targets. Summary Investigating the expression and location of mucin in nasal mucosa and understanding the role of various inflammatory factors in mucin expression are helpful to figure out regulatory mechanisms of airway mucin hypersecretion. It is of great significance for the treatment of CRS.

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Interleukin-Mediated Pendrin Transcriptional Regulation in Airway and Esophageal Epithelia

Cited by 8 publications

References 172 publications

Neuropeptide regulation of secretion and inflammation in human airway gland serous cells

Neuropeptide regulation of secretion and inflammation in human airway gland serous cells

Multivariate gene expression‐based survival predictor model in esophageal adenocarcinoma

Expression and Clinical Significance of Mucin Gene in Chronic Rhinosinusitis

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