Increased expression of hCLCA1 in chronic rhinosinusitis and its contribution to produce MUC5AC

Kim, Ha Kyun; Kook, Jin Ho; Kang, Ka Ram; Oh, Dong Ju; Kim, Tae Hoon; Lee, Sang Hag

doi:10.1002/lary.26109

Cited by 12 publications

(20 citation statements)

References 52 publications

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“…However, the mechanism underlying MU5AC overexpression in CRS patients remains unclear. 9,31,32 As early as 1999, Voynow et al 13 proposed that HNE may increase the mRNA and protein expression of MU5AC in airway epithelial cells. Human bronchial epithelial cells and human lung cancer cells were shown to have high levels of HNE-induced MUC5AC expression.…”

Section: Discussionmentioning

confidence: 99%

Human Neutrophil Elastase Induces MUC5AC Overexpression in Chronic Rhinosinusitis Through miR-146a

Yan

Zhang

et al. 2019

Am J Rhinol�Allergy

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Background The pathogenesis of chronic rhinosinusitis (CRS) is not yet clear. microRNAs are widely involved in a number of physiological and pathological processes, of which microRNA-146a (miR-146a) plays an important role in innate immunity, inflammatory response, and other pathophysiological processes. Mucins (MUCs) are important components of secreted mucus, of which MUC5AC is the major MUC secreted in the normal airway. Objective This study was performed to examine human neutrophil elastase (HNE)-induced MUC5AC overexpression in CRS via miR-146a. Methods miR-146a, HNE, epidermal growth factor receptor (EGFR), and MUC5AC expression in the sinonasal mucosa were determined using quantitative real-time polymerase chain reaction (qRT-PCR). EGFR, phosphorylated EGFR (pEGFR), and MUC5AC expression were determined in primary cultures of human nasal epithelial cells (HNECs). We examined the expression of miR-146a, MUC5AC, EGFR, and pEGFR by transfecting HNECs with miR-146a mimics and negative control (NC). Moreover, dual-luciferase reporter gene assays were used to validate EGFR as an hsa-miR-146a target gene. Results miR-146a was significantly downregulated, and HNE, EGFR, and MUC5AC were upregulated in CRS patients both with and without nasal polyps. In the in vitro cell experiment, MUC5AC was significantly downregulated after use of an EGFR-specific inhibitor (AG1478). Upon addition of miR-146a inhibitor, miR-146a was downregulated, while MUC5AC was upregulated. MUC5AC was suppressed in normal primary HNECs by miR-146a mimic and pEGFR was downregulated. The results of dual-luciferase reporter assays showed that the luciferase activities were markedly inhibited in the pGL3-EGFR-3′ UTR+miR-146a mimic group compared with the pGL3+ miR-146a mimic group, suggesting that EGFR is a target gene for miR-146a. Conclusion In HNE-induced CRS, miR-146a downregulates the expression of MUC5AC by inhibiting the activation of EGFR, and EGFR is a target gene of miR-146a.

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Section: Discussionmentioning

confidence: 99%

Human Neutrophil Elastase Induces MUC5AC Overexpression in Chronic Rhinosinusitis Through miR-146a

Yan

Zhang

et al. 2019

Am J Rhinol�Allergy

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“…Mucus hypersecretion is major symptom in CRSwNP patients. And hyperplasia of mucous glands and increase in goblet cells are common histological changes in NP [ 1 , 2 ]. Mucins are major component responsible for mucus secretion.…”

Section: Discussionmentioning

confidence: 99%

“…And overproduction of airway mucins is an important feature, which leads to an increase in the morbidity and mortality of inflammatory respiratory diseases [ 3 , 4 ]. In the studies on mucin gene expression in NP, MUC5AC overexpression was observed in sinonasal mucosa of CRSwNP and MUC5AC was expressed 4-fold higher than MUC2 and 12-fold higher than MUC1 in NP [ 2 , 17 ]. The excessive production of MUC5AC was well known to mediated by many inflammatory mediators, cytokines, and hormones [ 16 , 18 - 20 ].…”

Section: Discussionmentioning

confidence: 99%

“…Chronic rhinosinusitis (CRS) is a broad clinical syndrome that is defined by mucosal inflammation of the nose and paranasal sinuses, which is subdivided into two groups based the presence or absence of nasal polyps (NP). Among them, chronic rhinosinusitis with nasal polyps (CRSwNP) is one of the most difficult upper airway diseases to treat [ 1 , 2 ]. In CRSwNP, mucus hypersecretion is major symptom, which is associated with goblet cell metaplasia and hypertrophy of nasal airway epithelium.…”

Section: Introductionmentioning

confidence: 99%

“…Mucins are high molecular weight glycoproteins, one of major components responsible for mucus secretion, impart different physical and biological properties to mucus of the airway [ 3 , 4 ]. Among the mucins, MUC5AC is suggested to be a main marker of mucous metaplasia in sinonasal mucosa and predominant expressed in CRSwNP patients [ 2 ]. Nevertheless, the mechanisms underlying overproduction of MUC5AC glycoprotein in CRSwNP are not fully understood.…”

Section: Introductionmentioning

confidence: 99%

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Clusterin Induces MUC5AC Expression via Activation of NF-κB in Human Airway Epithelial Cells

Bae

Choi

et al. 2018

Clin Exp Otorhinolaryngol

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Objectives Clusterin (CLU) is known as apolipoprotein J, and has three isoforms with different biological functions. CLU is associated with various diseases such as Alzheimer disease, atherosclerosis, and some malignancies. Recent studies report an association of CLU with inflammation and immune response in inflammatory airway diseases. However, the effect of CLU on mucin secretion of airway epithelial cells has not yet been understood. Therefore, the effect and brief signaling pathway of CLU on MUC5AC (as a major secreted mucin) expression were investigated in human airway epithelial cells.Methods In the tissues of nasal polyp and normal inferior turbinate, the presence of MUC5AC and CLU was investigated using immunohistochemical stain and Western blot analysis. In mucin-producing human NCI-H292 airway epithelial cells and primary cultures of normal nasal epithelial cells, the effect and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling pathway of CLU on MUC5AC expression were investigated using immunohistochemical stain, reverse transcription-polymerase chain reaction, real-time polymerase chain reaction, enzyme immunoassay, and Western blot analysis.Results In the nasal polyps, MUC5AC and CLU were abundantly present in the epithelium on immunohistochemical stain, and nuclear CLU (nCLU) was strongly detected on Western blot analysis. In human NCI-H292 airway epithelial cells or the primary cultures of normal nasal epithelial cells, recombinant nCLU increased MUC5AC expression, and significantly activated phosphorylation of NF-κB. And BAY 11-7085 (a specific NF-κB inhibitor) and knockdown of NF-κB by NF-κB siRNA (small interfering RNA) significantly attenuated recombinant nCLU-induced MUC5AC expression.Conclusion These results suggest that nCLU induces MUC5AC expression via the activation of NF-κB signaling pathway in human airway epithelial cells.

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Characteristics of mucin hypersecretion in different inflammatory patterns based on endotypes of chronic rhinosinusitis

Zhai,

Shao,

et al. 2024

Clinical & Translational All

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BackgroundChronic rhinosinusitis (CRS) is usually accompanied by mucin hypersecretion that can lead to mucus accumulation and impair nasal mucociliary clearance, thus exacerbating airway inflammation. Abnormal mucin hypersecretion is regulated by different T helper (Th) cytokines, which are associated with different endotype‐driven inflammatory responses. Therefore, it is of great significance to understand how these factors regulate mucin hypersecretion to provide precise treatment strategies for different endotypes of CRS.BodyThus far, the most common endotypes of CRS are classified as type 1, type 2, or type 3 immune responses based on innate and adaptive cell‐mediated effector immunity, and the representative Th cytokines in these immune responses, such as IFN‐γ, TNF‐α, IL‐4, IL‐5, IL‐13, IL‐10, IL‐17, and IL‐22, play an important regulatory role in mucin secretion. We reviewed all the related literature in the PubMed database to determine the expression of these Th cytokines in CRS and the role they play in the regulation of mucin secretion.ConclusionWe believe that the main Th cytokines involved in specific endotypes of CRS play a key role in regulating abnormal mucin secretion, which contributes to better understanding of the pathogenesis of CRS and provides therapeutic targets for airway inflammatory diseases associated with mucin hypersecretion.

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Increased expression of hCLCA1 in chronic rhinosinusitis and its contribution to produce MUC5AC

Abstract: NA Laryngoscope, 126:E347-E355, 2016.

Cited by 12 publications

References 52 publications

Human Neutrophil Elastase Induces MUC5AC Overexpression in Chronic Rhinosinusitis Through miR-146a

Human Neutrophil Elastase Induces MUC5AC Overexpression in Chronic Rhinosinusitis Through miR-146a

Clusterin Induces MUC5AC Expression via Activation of NF-κB in Human Airway Epithelial Cells

Characteristics of mucin hypersecretion in different inflammatory patterns based on endotypes of chronic rhinosinusitis

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