Differential Expression of TFF1 and TFF3 in Patients Suffering from Chronic Rhinosinusitis with Nasal Polyposis

Mihalj, Martina; Bujak, Maro; Butković, Josip; Zubčić, Željko; Levak, Maja Tolušić; Ces, J.A.; Kopić, Vlatko; Lončar, Mirela Baus; Mihalj, Hrvoje

doi:10.3390/ijms20215461

Cited by 13 publications

(13 citation statements)

References 38 publications

(55 reference statements)

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“…Previous work using immunostaining approaches demonstrated that TFF1 and TFF3 are associated with allergic rhinitis and CRSsNP, whereas TFF2 was largely undetectable 9, 25 . In addition, measuring TFF1 and TFF3 mRNA levels in the sinonasal mucosa of CRSwNP patients revealed a significant upregulation of TFF3 gene expression concomittant with downregulation of TFF1 gene expression 10 . TFF1 and TFF3 are known products of goblet cells in both healthy and inflamed sinonasal tissues, TFF3 was also produced by ciliated epithelial cells, and submucosal glandular cells 25, 26 .…”

Section: Discussionmentioning

confidence: 94%

“…In the context of CRS, increased gene expression levels for TFF1 and 3 in the sinonasal mucosa has been reported for the Type 1 associated CRSsNP subtype 9 . Moreover, increased TFF3 with concomittant decreased TFF1 gene expression levels in the sinonasal mucosa has been reported for the Type 2 associated CRSwNP subtype 10 . TFFs are expressed in healthy and diseased tissue in human and mouse models and correlate with disease severity in asthma and COPD 11, 12 .…”

Section: Introductionmentioning

confidence: 90%

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Trefoil factor 3 positively associates with IL-25 in patients with Chronic Rhinosinusitis

Ortiz-Carpena

Maina

Lin

et al. 2020

Preprint

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Background Trefoil factor family cytokines (TFF1-3) have documented reparative and immunoregulatory effects on mucosal epithelial cells that include: blocking apoptosis, directed cell migration, and regulation of pro-inflammatory cytokine production. TFF1 and TFF3 have been shown to undergo altered expression within sinonasal tissues of patients with various forms of chronic rhinosinusitis including those with or wthout polyp associated disease, but the cellular source(s) of TFF members in CRS remains unclear. To further explore the role of TFF3 in inflammatory sinonasal disease, we sought to determine its expression pattern in immune and non-immune cell types in CRS disease. Methods Polyp and inferior turbinate tissues were isolated from patients undergoing surgical resection for treatment of CRS. Tissue homogenates and single cell suspensions were subjected to enzyme linked immunosorbent assay (ELISA) and single-cell RNA sequencing. Air liquid interface cultures of sinonasal epithelia were subjected to immunofluorescence (IF) microscopy. Interleukin 25, TFF2 and TFF3 protein levels were compared to sinonasal outcome test scores (SNOT-22) to determine whether levels associated with post-operative outcomes. Results TFF3 was broadly expressed in goblet cells, ciliated cells, Tuft cells and T lymphocytes. TFF3 protein levels positively associated with IL-25 in CRSwNP patients. Lastly, TFF3 protein levels positively associated with clinical improvement post-surgery. Conclusions TFF3 is broadly expressed within multiple epithelial and immune cell lineages in patients with CRSwNP. Protein levels of TFF3 correlate with IL-25 and clinical signs of disease, however TFF3 levels associate with clinical improvement following surgical intervention indicating a potential beneficial role for this reparative cytokine in CRS patients.

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Section: Discussionmentioning

confidence: 94%

Section: Introductionmentioning

confidence: 90%

Trefoil factor 3 positively associates with IL-25 in patients with Chronic Rhinosinusitis

Ortiz-Carpena

Maina

Lin

et al. 2020

Preprint

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“…Some of these genes (MUC5B, TFF1, and TFF3) were previously shown to be over-expressed in middle turbinate samples from patients with CRS. 39,40 (which was not certified by peer review) is the author/funder. All rights reserved.…”

Section: Serous Cellsmentioning

confidence: 99%

Cell type catalog of middle turbinate epithelium

Mathews

Tung

Foronjy

et al. 2022

Preprint

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Importance: Elucidation of the cellular makeup of the middle turbinate provides a foundation for future studies of pathogenesis of sinonasal disease. Neural progenitors and pluripotent basal cells found in middle turbinate mucosa potentially can be used to develop cellular models to study brain disorders or in regenerative medicine to substitute neuronal tissues. Objective: Single cell RNA-sequencing (scRNA-seq) of middle turbinate mucosa was performed to create the first single cell transcriptome catalog of this part of the human body. Design: Samples were obtained from the head of the middle turbinate from healthy volunteers. After the specimen was prepared per lab protocol, cells were dissociated, suspended, and counted. Single cell libraries were then prepared according to the 10x Genomics protocol and sequenced using NovaSeq 6000 (Illumina). Sequencing data were processed using Cell Ranger, and clustering and gene expression analysis was performed using Seurat. Cell types were annotated using known markers and data from other single cell studies. Setting: Single center, tertiary care center Participants: Healthy volunteer. Intervention(s) (for clinical trials) or Exposure(s) (for observational studies): None. Main Outcome(s) and Measure(s): Identification of cell types of middle turbinate mucosa through expression profiling of single cells using known markers. Results: 14 unique cell types were identified, including serous, goblet, club, basal, ciliated, endothelial, and neural progenitor cells, as well as multiple types of blood cells. Conclusions and Relevance: This catalog provides a comprehensive depiction of the cellular composition of middle turbinate mucosa. By uncovering the cellular stratification of gene expression profiles in healthy middle turbinate epithelium, the groundwork has been laid for further investigation into the molecular pathogenesis and targeted therapy of sinonasal disease.

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“…Ciliated cells are responsible for mucociliary clearance. All airway secretory cell types differentiate from airway epithelial cells [ 23 , 24 , 25 ]. The airway mucus consists of a sol layer and a gel layer that together form a defense barrier termed the “cilia-mucus blanket” [ 26 , 27 ].…”

Section: The Biological Characteristics Of Mucinsmentioning

confidence: 99%

The Potential Role and Regulatory Mechanisms of MUC5AC in Chronic Obstructive Pulmonary Disease

2020

Molecules

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Chronic obstructive pulmonary disease (COPD) is associated with high morbidity and mortality globally. Studies show that airway mucus hypersecretion strongly compromises lung function, leading to frequent hospitalization and mortality, highlighting an urgent need for effective COPD treatments. MUC5AC is known to contribute to severe muco-obstructive lung diseases, worsening COPD pathogenesis. Various pathways are implicated in the aberrant MUC5AC production and secretion MUC5AC. These include signaling pathways associated with mucus-secreting cell differentiation [nuclear factor-κB (NF-κB)and IL-13-STAT6- SAM pointed domain containing E26 transformation-specific transcription factor (SPDEF), as well as epithelial sodium channel (ENaC) and cystic fibrosis transmembrane conductance regulator (CFTR)], and signaling pathways related to mucus transport and excretion-ciliary beat frequency (CBF). Various inhibitors of mucus hypersecretion are in clinical use but have had limited benefits against COPD. Thus, novel therapies targeting airway mucus hypersecretion should be developed for effective management of muco-obstructive lung disease. Here, we systematically review the mechanisms and pathogenesis of airway mucus hypersecretion, with emphasis on multi-target and multi-link intervention strategies for the elucidation of novel inhibitors of airway mucus hypersecretion.

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Differential Expression of TFF1 and TFF3 in Patients Suffering from Chronic Rhinosinusitis with Nasal Polyposis

Cited by 13 publications

References 38 publications

Trefoil factor 3 positively associates with IL-25 in patients with Chronic Rhinosinusitis

Trefoil factor 3 positively associates with IL-25 in patients with Chronic Rhinosinusitis

Cell type catalog of middle turbinate epithelium

The Potential Role and Regulatory Mechanisms of MUC5AC in Chronic Obstructive Pulmonary Disease

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