Epithelial Tight Junction Anomalies in Nasal Inverted Papilloma

Abstract

ObjectivesAs a critical component of the epithelial barrier, tight junctions (TJs) are essential in nasal mucosa against pathogen invasion. However, the function of TJs has rarely been reported in nasal inverted papilloma (NIP). This study aims to investigate the potential factors of TJs' abnormality in NIP.MethodsWe assessed the expression of ZO‐1, occludin, claudin‐1, claudin‐3, and claudin‐7 in healthy controls and NIP by real‐time quantitative polymerase chain reaction and immunofluorescent staining. The correlation between TJs expression and neutrophil count, TH1/TH2/TH17 and regulatory T cell biomarkers, and the proportion of nasal epithelial cells was investigated.ResultsUpregulation of ZO‐1, occludin, claudin‐1, and claudin‐7, along with downregulation of claudin‐3, was found in NIP compared to control (all p < 0.05). An abnormal proportion with a lower number of ciliated cells (control vs. NIP: 37.60 vs. 8.67) and goblet cells (12.52 vs. 0.33) together with a higher number of basal cells (45.58 vs. 124.00) in NIP. Meanwhile, claudin‐3 was positively correlated with ciliated and goblet cells (all p < 0.01). Additionally, neutrophils were excessively infiltrated in NIP, negatively correlated with ZO‐1, but positively with claudin‐3 (all p < 0.05). Furthermore, FOXP3, IL‐10, TGF‐β1, IL‐5, IL‐13, and IL‐22 levels were induced in NIP (all p < 0.01). Occludin level was negatively correlated with IL‐10, IL‐5, IL‐13, and IL‐22, whereas ZO‐1 was positively with TGF‐β1 (all p < 0.05).ConclusionNasal epithelial barrier dysfunction with TJs anomalies is commonly associated with abnormal proliferation and differentiation of epithelial cells and imbalance of immune and inflammatory patterns in NIP.Level of EvidenceNA Laryngoscope, 2023

Updated epithelial barrier dysfunction in chronic rhinosinusitis: Targeting pathophysiology and treatment response of tight junctions

“…35,50,63,[71][72][73][74][75][76][77] In contrast, claudin-4 71,78-81 and claudin-7 71,77,80,81 exhibited a more widespread expression pattern throughout the nasal epithelium, spanning from the apical to basal regions. Additionally, several studies have reported that RHOA 78 and claudin-10 63 are expressed throughout the nasal epithelium, whereas claudin-3 35,63,77 is predominantly localized to the surface of ciliated cells in the uppermost layer. Controversially, occludin can be found either at the apical 50,72,73,76,82,83 or throughout the nasal epithelium, 35,63,71,75,77,84 JAM-A 71,76,85 and tricellulin 63,83,86,87 are similar expressed to occludin.…”

“…Consistently, ZO-1 was predominantly expressed at the apical region of nasal epithelial cells. 35,50,63,[71][72][73][74][75][76][77] In contrast, claudin-4 71,78-81 and claudin-7 71,77,80,81 exhibited a more widespread expression pattern throughout the nasal epithelium, spanning from the apical to basal regions. Additionally, several studies have reported that RHOA 78 and claudin-10 63 are expressed throughout the nasal epithelium, whereas claudin-3 35,63,77 is predominantly localized to the surface of ciliated cells in the uppermost layer.…”

“…ZO-1 Apical layer: Soyka, 50 Huang, 35,63,77 Takano, 71 Steelant, 72,73 Jang, 74 Tian, 75 Zuckerman 76 Occludin Apical layer: Soyka, 50 Steelant, 72, 73 Zuckerman, 76 Doulaptsi, 82 Ohkuni 83 Full epithelium: Huang, 35,63,77 Takano, 71 Tian, 75 Rogers 84 JAM-A Apical layer: Takano 71 Full epithelium: Zuckerman, 76 Wise 85 Tricellulin Apical layer: Suzuki 86 Full epithelium: Ohkuni, 83 Nguyen, 87 Huang 63 RHOA Full epithelium: Kaneko 78 Claudin-1 Basal Layer: Takano, 71 Suzuki, 86 Huang 63,77 Full epithelium: Tian, 75 Kaneko, 81 Rogers 84 Claudin-3 Full epithelium: Huang 35,63,77 Claudin-4 Full epithelium: Takano, 71 Kaneko, 78,81 Zhang, 79 Altunbulakli 80 Claudin-7 Full epithelium: Takano, 71 Altunbulakli, 80 Kaneko, 81 Huang 77 Claudin-10 Full epithelium: Huang…”

“…Additionally, several studies have reported that RHOA 78 and claudin-10 63 are expressed throughout the nasal epithelium, whereas claudin-3 35,63,77 is predominantly localized to the surface of ciliated cells in the uppermost layer. Controversially, occludin can be found either at the apical 50,72,73,76,82,83 or throughout the nasal epithelium, 35,63,71,75,77,84 JAM-A 71,76,85 and tricellulin 63,83,86,87 are similar expressed to occludin. Interestingly, claudin-1 may exhibit either basal cellspecific localization 63,71,77,86 or diffuse distribution throughout the entire epithelial layer.…”

“…Controversially, occludin can be found either at the apical 50,72,73,76,82,83 or throughout the nasal epithelium, 35,63,71,75,77,84 JAM-A 71,76,85 and tricellulin 63,83,86,87 are similar expressed to occludin. Interestingly, claudin-1 may exhibit either basal cellspecific localization 63,71,77,86 or diffuse distribution throughout the entire epithelial layer. 75,81,84 The inconsistency in the localization of TJs expression may be attributed to interindividual variations in the tested samples and inconsistent experimental conditions, such as differences in antigen retrieval methods.…”