Eosinophils Correlate with Epithelial-Mesenchymal Transition in Chronic Rhinosinusitis with Nasal Polyps

ORL ◽  
2021 ◽  
pp. 1-11
Author(s):  
Mingjie Wang ◽  
Yan Sun ◽  
Cheng Li ◽  
Jing Qu ◽  
Bing Zhou
Keyword(s):  
Epithelial Cells ◽  
Chronic Rhinosinusitis ◽  
Nasal Polyps ◽  
Epithelial Mesenchymal Transition ◽  
Airway Remodeling ◽  
Eosinophil Infiltration ◽  
Control Group ◽  
Epithelial Tissue ◽  
Mesenchymal Transition ◽  
Eosinophilic Chronic Rhinosinusitis

<b><i>Introduction:</i></b> Chronic inflammation and tissue remodeling always occur together in chronic rhinosinusitis (CRS). Epithelial-mesenchymal transition (EMT) plays a critical role in airway remodeling. <b><i>Objective:</i></b> Changes of epithelial cells in sinus mucosa in different subtypes of CRS, especially in eosinophilic chronic rhinosinusitis with nasal polyps, and the role of EMT and eosinophils (EOS) in airway remodeling are still unknown. <b><i>Methods:</i></b> We included 85 patients in this study. They were divided into 4 groups: a normal control (NC) group, a chronic rhinosinusitis without nasal polyps (CRSsNP) group, an eosinophilic chronic rhinosinusitis with nasal polyps (ECRSwNP) group, and a noneosinophilic chronic rhinosinusitis with nasal polyps (non-ECRSwNP) group. Clinical data were all collected and analyzed. Standard hematoxylin and eosin staining, immunohistochemical staining, and 2-color immunofluorescence staining were performed. Biomarkers of EMT, epithelial cadherin, and vimentin were labeled. The immunohistochemistry results of each group were counted and statistically analyzed. <b><i>Results and Conclusion:</i></b> E-cadherin was downregulated, and vimentin was upregulated in epithelial tissue from the ECRSwNP group, compared with that from the control group and the other groups. The number of vimentin-expressing epithelial cells correlated with sinus CT imaging Lund-Mackay scores (<i>r</i> = 0.560, <i>p</i> &#x3c; 0.001). Moreover, expression levels of vimentin in the epithelium were associated with numbers of infiltrating EOS in tissues (<i>r</i> = 0.710, <i>p</i> &#x3c; 0.001) and the peripheral blood EOS ratio (<i>r</i> = 0.594, <i>p</i> &#x3c; 0.001). EMT occurred in patients with CRSwNP, especially in those with ECRSwNP. Epithelial reprogramming correlates with eosinophil infiltration and disease severity. Eosinophils contributed to impairment of epithelial function and promoted EMT in CRSwNP.

Interleukin-27 Inhibits Epithelial-Mesenchymal Transition in Ovalbumin-Induced Mice Bronchial Epithelial Cells

2021 ◽  
Vol 11 (6) ◽  
pp. 1129-1137
Author(s):  
Yuanyuan Liu ◽  
Chao He ◽  
Xin Li ◽  
Zewen Zhang ◽  
Ju Liu ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Epithelial Mesenchymal Transition ◽  
Airway Remodeling ◽  
Bronchial Epithelial Cell ◽  
Phenotypic Marker ◽  
Bronchial Epithelial ◽  
Mesenchymal Transition ◽  
Stat3 Phosphorylation

The epithelial-mesenchymal transition (EMT) of bronchial epithelial cells is a critical mechanism involved in transforming growth factor beta 1 (TGF-β1) induced asthma airway remodeling. Previous study has shown that interleukin 27 (IL-27) attenuates EMT in alveolar epithelial cells, but its effects on the BEAS-2B human bronchial epithelial cell line EMT remain unknown. Herein, we explored the effects of IL-27 on BEAS-2B EMT in vivo and in vitro. In the in vivo experiments, we found that IL-27 nose-drip therapy alleviated airway remodeling, increased the epithelial phenotypic marker epithelial-cadherin (E-cadherin), and decreased the mesenchymal phenotypic marker alpha-smooth muscle actin (α-SMA) compared with the asthmatic control group. We also found that IL-27 suppressed the signal transducer and activator of transcription (STAT3) in the lung tissue of asthmatic mice. in vitro, TGF-β1-induced EMT changes, including downregulation of E-cadherin and upregulation of α-SMA, were suppressed by IL-27 treatment. Additionally, STAT3 phosphorylation was activated by TGF-β1, whereas IL-27 inhibited the activation of TGF-β1 induced STAT3 phosphorylation. Our findings indicated that IL-27 could inhibit airway remodeling by attenuating bronchial epithelial cell EMT in vivo and in vitro. Therefore, IL-27 may be a beneficial therapeutic option targeting asthmatic airway remodeling.

scholarly journals Nasal Polyposis: Insights in Epithelial-Mesenchymal Transition and Differentiation of Polyp Mesenchymal Stem Cells

2020 ◽  
Vol 21 (18) ◽  
pp. 6878 ◽  
Author(s):  
Emanuela Chiarella ◽  
Nicola Lombardo ◽  
Nadia Lobello ◽  
Annamaria Aloisio ◽  
Teodoro Aragona ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Chronic Rhinosinusitis ◽  
Nasal Polyps ◽  
Inflammatory Process ◽  
Nasal Polyposis ◽  
Epithelial Mesenchymal Transition ◽  
Nasal Congestion ◽  
Alternative Source ◽  
Mesenchymal Transition

Chronic rhinosinusitis is a common inflammatory disease of paranasal sinuses, which causes rhinorrhea, nasal congestion, and hyposmia. The genetic predisposition or the exposure to irritants can sustain the inflammatory response and the development of nasal polyposis. Nasal polyps are benign and teardrop-shaped growths that project in the nasal cavities, and originate from the ethmoid sinuses. This inflammatory process is associated with high expression of IL-4, IL-5 and IL-13 and IgE. Antibodies targeting these cytokines or receptors represent a therapeutic strategy in the treatment of nasal polyposis in combination with corticosteroids. The molecular pathogenesis of nasal polyps in chronic rhinosinusitis (CRS) patients is associated with remodeling transition, a process in which epithelial cells lose their typical phenotype, acquiring a mesenchymal-like aspect. TGFβ/SMAD, ERK, and Wnt/β-catenin pathways are altered during the nasal tissue remodeling. miRNA and inhibitor molecules targeting these signaling pathways are able to interfere with the process; which could lead to alternative therapies. Nasal polyps are an alternative source of mesenchymal stem cells, which can be isolated from surgical biopsies. A molecular understanding of the biology of PO-MSCs will contribute to the delineating inflammatory process underlying the development of nasal polyps.

scholarly journals Epithelial–mesenchymal transition: role in cancer progression and the perspectives of antitumor treatment

Acta Naturae ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 4-23
Author(s):  
A. V. Gaponova ◽  
S. Rodin ◽  
A. A. Mazina ◽  
P. V. Volchkov
Keyword(s):  
Epithelial Cells ◽  
Tumor Progression ◽  
Cancer Progression ◽  
Molecular Mechanisms ◽  
Epithelial Mesenchymal Transition ◽  
Malignant Tumors ◽  
The Body ◽  
Epithelial Tissue ◽  
Mesenchymal Transition ◽  
Tumor Dissemination

About 90% of all malignant tumors are of epithelial nature. The epithelial tissue is characterized by a close interconnection between cells through cellcell interactions, as well as a tight connection with the basement membrane, which is responsible for cell polarity. These interactions strictly determine the location of epithelial cells within the body and are seemingly in conflict with the metastatic potential that many cancers possess (the main criteria for highly malignant tumors). Tumor dissemination into vital organs is one of the primary causes of death in patients with cancer. Tumor dissemination is based on the so-called epithelialmesenchymal transition (EMT), a process when epithelial cells are transformed into mesenchymal cells possessing high mobility and migration potential. More and more studies elucidating the role of the EMT in metastasis and other aspects of tumor progression are published each year, thus forming a promising field of cancer research. In this review, we examine the most recent data on the intracellular and extracellular molecular mechanisms that activate EMT and the role they play in various aspects of tumor progression, such as metastasis, apoptotic resistance, and immune evasion, aspects that have usually been attributed exclusively to cancer stem cells (CSCs). In conclusion, we provide a detailed review of the approved and promising drugs for cancer therapy that target the components of the EMT signaling pathways.

scholarly journals S100A8 Enhances IL-1β Production from Nasal Epithelial Cells in Eosinophilic Chronic Rhinosinusitis

2021 ◽  
Author(s):  
Ayaka Nakatani ◽  
Takeshi Tsuda ◽  
Yohei Maeda ◽  
Masaki Hayama ◽  
Daisuke Okuzaki ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Chronic Rhinosinusitis ◽  
Nasal Polyps ◽  
Expression Profiles ◽  
Allergic Inflammation ◽  
Gene Expression Profiles ◽  
Interleukin 1Β ◽  
Nasal Epithelial Cells ◽  
Human Nasal Epithelial Cells ◽  
Eosinophilic Chronic Rhinosinusitis

Abstract Chronic rhinosinusitis is classified into eosinophilic chronic rhinosinusitis (ECRS) and non-eosinophilic chronic rhinosinusitis (NECRS). ECRS is a refractory allergic disease involving a variety of immune and epithelial cells. S100A8 is a damage-associated molecular pattern that is closely related to allergic inflammation. However, the pathological implications of S100A8 in ECRS have not been clarified. We evaluated the role of S100A8 in the pathogenesis of ECRS. Gene expression profiles of nasal polyps obtained from patients with ECRS or NECRS were evaluated using RNA sequencing. S100A8 was identified as a significantly upregulated gene in nasal polyps associated with ECRS. Immunohistochemistry consistently revealed intense S100A8 staining in nasal polyps from patients with ECRS. Human nasal epithelial cells expressed the receptor for advanced glycation end products and Toll-like receptor 4. Recombinant S100A8 protein induced interleukin-1β secretion in human nasal epithelial cells. Our data demonstrate that S100A8 results in production of interleukin-1β in the nasal epithelium, which may be involved in the pathogenesis of ECRS.

scholarly journals Deficit in Adipose Differentiation in Mesenchymal Stem Cells Derived from Chronic Rhinosinusitis Nasal Polyps Compared to Nasal Mucosal Tissue

2020 ◽  
Vol 21 (23) ◽  
pp. 9214
Author(s):  
Emanuela Chiarella ◽  
Nicola Lombardo ◽  
Nadia Lobello ◽  
Giovanna Lucia Piazzetta ◽  
Helen Linda Morrone ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Chronic Rhinosinusitis ◽  
Nasal Mucosa ◽  
Nasal Polyps ◽  
Epithelial Mesenchymal Transition ◽  
Nasal Congestion ◽  
Normal Mucosa ◽  
Molecular Response ◽  
Mesenchymal Transition

Chronic rhinosinusitis of the nasal mucosa is an inflammatory disease of paranasal sinuses, which causes rhinorrhea, nasal congestion, and hyposmia, and in some cases, it can result in the development of nasal polyposis. Nasal polyps are benign lobular-shaped growths that project in the nasal cavities; they originate from inflammation in the paranasal mucous membrane and are associated with a high expression of interleukins (IL)-4, IL-5, IL-13, and IgE. Polyps derive from the epithelial–mesenchymal transition of the nasal epithelium resulting in a nasal tissue remodeling. Nasal polyps from three patients with chronic rhinosinusitis as well as control non-polyp nasal mucosa were used to isolate and cultivate mesenchymal stem cells characterized as CD73+, CD90+, CD105+/CD14−, CD34−, and CD45−. Mesenchymal stem cells (MSCs) cultures were induced to differentiate toward adipocytes, where lipid droplets and adipocyte genes PPARγ2, ADIPO-Q, and FABP4 were observed in control non-polyp nasal mucosa-derived mesenchymal cells but were scarcely present in the cultures derived from the nasal polyps, where apoptosis was evident. The modulation of the response to adipogenic stimulus in polyps represents a change in the molecular response that controls the cascade required for differentiation as well as possible means to specifically target these cells, sparing the normal mucosa of the nasal sinuses.

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