Relationship between epithelial damage or basement membrane thickness and eosinophilic infiltration in nasal polyps with chronic rhinosinusitis

Saitoh, Tatsuya; Kusunoki, Takeshi; Yao, Toru; Kawano, Kenji; Kojima, Yuko; Miyahara, Katsumi; Onoda, Junko; Yokoi, Hidenori; Ikeda, Katsuhisa

doi:10.4193/rhin08.109

Cited by 51 publications

(38 citation statements)

References 33 publications

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“…D, the quantitative analysis of 10 samples from each group showed that the mean BM thickness was higher in the ECRSwNP group than that in the nonECRSwNP group and the HC group (both p < 0.001). Thus, CRSwNP infiltrated with eosinophils showed a higher BM thickness in the Chinese population, which is consistent with previous results reported in Japan and Australia . Moreover, the BM thickening indicated that the EMT was more pronounced in ECRSwNP than in nonECRSwNP or the controls.…”

Section: Resultssupporting

confidence: 91%

“…Recent evidence suggests that epithelial–mesenchymal transition (EMT); which is integral to development and can be reactivated in wound healing, fibrosis, and cancer progression, may also be involved in tissue remodeling in CRSwNP patients . Although chronic EMT is characterized by an expanded basement membrane (BM), changes in the expression of tissue remodeling‐related molecules including matrix metalloproteinase(MMP) family members and tissue inhibitor of metalloproteinases (TIMPs), soluble growth factors or cytokines including transforming growth factor‐β (TGF‐β) family members, T‐helper 2 (Th2)‐type cytokines, and inflammatory cells such as eosinophils, the mechanisms involved in ECM in CRSwNP are not fully understood.…”

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confidence: 99%

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Inhibition of arachidonate 15‐lipoxygenase reduces the epithelial–mesenchymal transition in eosinophilic chronic rhinosinusitis with nasal polyps

Yan

Wang

et al. 2018

Int Forum Allergy Rhinol

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Background:The epithelial-mesenchymal transition (EMT) is a distinguishing characteristic of chronic rhinosinusitis with nasal polyps (CRSwNP). The underlying mechanism remains largely unknown. Arachidonate 15lipoxygenase (ALOX15), an enzyme involved in arachidonic acid metabolism, has been reported to cause airway epithelial injury and thus may further promote the EMT. The aim of this study was to evaluate the role of ALOX15 during the EMT process in CRSwNP. Methods:A total of 54 samples were obtained, including 10 from healthy control, 16 from non-eosinophilic CRSwNP, and 28 from eosinophilic CRSwNP. Hematoxylin and eosin staining was performed to determine the basement membrane (BM) thickness. The concentration of molecules mediating remodeling was assayed by Luminex. The messenger RNA (mRNA) and protein levels of target genes were measured by quantitative real-time polymerase chain reaction (PCR) and Western blo ing.Results: EMT was enhanced in eosinophilic CRSwNP compared with the healthy controls and non-eosinophilic CR-SwNP infiltrated with lymphocytes and/or plasma cells. The expression pa ern of molecules related to remodeling, including matrix metalloproteinases (MMPs), tissue inhibitor of metalloproteinases (TIMPs), and transforming growth factor β (TGF-β) family members, differed between the subtypes of CRSwNP. The mRNA level of ALOX15 was correlated with the BM thickness and MMP-1 and TGF-β3 expression. The inhibition of ALOX15 by PD146176 could induce claudin-1, claudin-4, claudin-7, zonula occludens (ZO)-1, ZO-2, E-Cadherin, TIMP-1, and TIMP-3 expressions and reduce the levels of MMP-1 and N-Cadherin in epithelial cells acquired from eosinophilic CRSwNP patients. Conclusion:The specific inhibition of ALOX15 could a enuate the EMT, which may provide an alternative method for the treatment of CRSwNP. C 2018 ARS-AAOA, LLC.

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Section: Resultssupporting

confidence: 91%

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confidence: 99%

Inhibition of arachidonate 15‐lipoxygenase reduces the epithelial–mesenchymal transition in eosinophilic chronic rhinosinusitis with nasal polyps

Yan

Wang

et al. 2018

Int Forum Allergy Rhinol

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“…We demonstrated an increase of squamous metaplasia and basement membrane thickening over time in Chinese patients with CRSwNP, which may be explained by the potential link between tissue eosinophilia and epithelial damage and basement membrane thickness (20) . Consistent with a previous study (10) , the number of glands was decreased over a 14-year period.…”

Section: Discussionmentioning

confidence: 71%

A retrospective study of changes of histopathology of nasal polyps in adult Chinese in central China

Jiang

Cao

et al. 2019

Rhin

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Background: The factors contributing to the eosinophilic inflammation in chronic rhinosinusitis with nasal polyps (CRSwNP) remain elusive. This study was designed to investigate the inflammatory patterns and tissue remodeling of CRSwNP in patients from central China at two time points over 14 years apart and the influence of age. Methods: One hundred and eight CRSwNP patients enrolled in 2000 and 2001 (group A), and 134 CRSwNP patients enrolled in 2014 and 2015 (group B) were retrospectively studied. Hematoxylin-eosin stained tissue sections were used to study characteristics of inflammation and tissue remodeling. Immunohistochemistry was used to further evaluate the cells positive for eosinophil cationic protein (ECP), IL-5, IgE, tryptase or myeloperoxidase (MPO). Time-and age-related difference was analyzed. Results: The number of eosinophils and proportion of eosinophilic CRSwNP were increased, whereas the numbers of total inflammatory cells and lymphocytes were decreased in group B as compared with group A. Group B had severer epithelial squamous metaplasia and basement membrane thickening, and a lower number of mucosal glands than group A. Higher numbers of ECP + , IL-5 + and IgE + cells were detected in group B than those in group A. The elderly (≥ 60 yrs) and non-elderly (< 60 yrs) had a comparable number of eosinophils and ratio of eosinophilic CRSwNP. Conclusion: Eosinophilic inflammation has been significantly augmented over time, which is associated with increased Th2 response and IgE production, and accompanied by exaggerated epithelium remodeling in CRSwNP patients from central China. Age has no significant influence on eosinophilic inflammation.

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“…40 Dysregulation of epithelium and morphological changes in NPs have been shown. 3,41 Prolonged inflammatory states also disrupt the balance of the coagulation and fibrinolysis cascades, leading to excessive fibrin deposition in the tissue. Takabayashi et al showed that excessive fibrin deposition is seen in NPs and that t-PA is downregulated in NPs, further demonstrating that IL-4 and IL-13 inhibit t-PA induction in airway epithelial cells.…”

Section: Discussionmentioning

confidence: 99%

Short‐chain fatty acids induce tissue plasminogen activator in airway epithelial cells via GPR41&43

Imoto

Kato

Takabayashi

et al. 2018

Clin Experimental Allergy

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Summary Background Chronic rhinosinusitis (CRS) is a heterogeneous chronic inflammatory disease generally divided based on the presence or absence of nasal polyps (NPs). One of the features of NPs is excessive fibrin deposition, which is associated with down-regulation of tissue plasminogen activator (t-PA) in NPs. As t-PA is expressed in epithelial cells, and epithelium is readily accessible to topical therapies, identifying compounds that can mediate the induction of t-PA would be a potential new strategy for the treatment of NPs. Objective The objective of this study was to determine whether short-chain fatty acids (SCFAs) can induce t-PA in airway epithelial cells via their known receptors GPR41 and GPR43. Methods We performed immunohistochemistry (IHC) to determine whether receptors for SCFAs, known as G protein-coupled receptor 41/free fatty acid receptor 3 (GPR41/FFAR3) and GPR43/FFAR2, are expressed in nasal tissue. Primary normal human bronchial epithelial (NHBE) cells were stimulated with different concentrations of SCFAs to test induction of t-PA, which was analysed by expression of mRNA and protein. Mediation of responses by SCFA receptors was evaluated by specific receptor gene silencing with siRNA. Results Immunohistochemistry study revealed that airway epithelial cells expressed GPR41 and GPR43. Acetic acid, propionic acid, butyric acid and valeric acid significantly induced t-PA expression from two- to tenfolds. The strongest inducer of t-PA from NHBE cells was propionic acid; cells stimulated with propionic acid released t-PA into the supernatant in its active form. Gene silencing of GPR41 and GPR43 revealed that induction of t-PA by SCFAs was dependent upon both GPR41 and GPR43. Conclusions and Clinical Relevance Short-chain fatty acids were shown to induce airway epithelial cell expression of t-PA via GPR41 and GPR43. Topical delivery of potent compounds that activate these receptors may have value by reducing fibrin deposition and shrinking nasal polyp growth.

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Relationship between epithelial damage or basement membrane thickness and eosinophilic infiltration in nasal polyps with chronic rhinosinusitis

Cited by 51 publications

References 33 publications

Inhibition of arachidonate 15‐lipoxygenase reduces the epithelial–mesenchymal transition in eosinophilic chronic rhinosinusitis with nasal polyps

Inhibition of arachidonate 15‐lipoxygenase reduces the epithelial–mesenchymal transition in eosinophilic chronic rhinosinusitis with nasal polyps

A retrospective study of changes of histopathology of nasal polyps in adult Chinese in central China

Short‐chain fatty acids induce tissue plasminogen activator in airway epithelial cells via GPR41&43

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