Sirtuin 1 attenuates nasal polypogenesis by suppressing epithelial-to-mesenchymal transition

Lee, Mingyu; Kim, Dae Woo; Yoon, Haejin; So, Daeho; Khalmuratova, Roza; Rhee, Chae Seo; Park, Jong-Wan; Shin, Hyun Woo

doi:10.1016/j.jaci.2015.07.026

Cited by 63 publications

(83 citation statements)

References 43 publications

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“…Group B was administered with the vehicle, i.e., PBS without RSV, and animals showed 5 or more nasal polyps in the sinonasal cavity. However, upon intranasal delivery of RSV solution (Group C), there was an apparent reduction in polyp number compared to that of Group B, in accordance with our previous results6. When the same amount of RSV was administered with PLGA/PEG NM (Group D), the number of polypoid lesions was further reduced compared to that of Group C (Fig.…”

Section: Resultssupporting

confidence: 90%

“…The nasal epithelium in Groups B and F showed markedly decreased E-cadherin expression compared to normal intact epithelium (Group A). However, upon administration of the RSV solution (Group C), E-cadherin expression remained high with respect to Groups B and F, indicating a marked reduction in polyp-formation capacity6. As anticipated, animals treated with RSV-loaded PLGA/PEG NM (Groups D and E) exhibited significantly greater E-cadherin expression.…”

Section: Resultsmentioning

confidence: 53%

“…To do so, we applied the RSV-loaded PLGA/PEG NM to a previously established murine nasal polyp model (Fig. 3A)561025. The polyp model was generated by chronic administration of ovalbumin (OVA) and Staphylococcus aureus enterotoxin B (SEB) (Groups B-F).…”

Section: Resultsmentioning

confidence: 99%

“…RSV is known to activate SIRT1, which then attenuates HIF-1α activity in nasal epithelial cells through deacetylation628. In this work, we assessed E-cadherin expression as a representative marker of HIF-1α activity.…”

Section: Resultsmentioning

confidence: 99%

“…Recently, we showed that hypoxia-inducible factor-1 (HIF-1) can induce the epithelial-to-mesenchymal transition (EMT) of the nasal polyp epithelium, leading to nasal polypogenesis5. Thereafter, we reported that Sirtuin 1 (SIRT1) can be considered a novel therapeutic target because of its suppression of HIF-1α-induced mucosal remodeling; thus, we proposed a SIRT1 activator, resveratrol, as a novel therapeutic agent6. Resveratrol (RSV), a naturally occurring polyphenolic compound, has received great attention for its anti-carcinogenic, anti-inflammatory and anti-oxidant effects789.…”

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confidence: 99%

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Sinonasal Delivery of Resveratrol via Mucoadhesive Nanostructured Microparticles in a Nasal Polyp Mouse Model

Lee

Park

Huh

et al. 2017

Sci Rep

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Resveratrol (RSV) has been shown to effectively suppress chronic rhinosinusitis with nasal polyps in a mouse model; however, when locally administered to the sinonasal cavity, bolus RSV is limited by low drug bioavailability owing to its low aqueous solubility and relatively rapid clearance from the administration site. To address this limitation, we propose mucoadhesive nanostructured microparticles (PLGA/PEG NM) as a potential carrier for the sinonasal delivery of RSV. In this study, PLGA/PEG NM released RSV in a sustained manner. Owing to the enlarged specific surface area of the nanostructures, PLGA/PEG NM had synergistically enhanced mucoadhesiveness and thus showed improved in vivo retention properties in the sinonasal cavity. Therefore, when tested in a mouse nasal polyp model, PLGA/PEG NM mitigated polyp formation and restored epithelial integrity better than the control treatments. The therapeutic effect was similar at half the dose of PLGA/PEG NM, suggesting improved local bioavailability of RSV in the sinonasal cavity.

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Section: Resultssupporting

confidence: 90%

Section: Resultsmentioning

confidence: 53%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

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Sinonasal Delivery of Resveratrol via Mucoadhesive Nanostructured Microparticles in a Nasal Polyp Mouse Model

Lee

Park

Huh

et al. 2017

Sci Rep

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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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miR‐200a‐3p regulates epithelial–mesenchymal transition and inflammation in chronic rhinosinusitis with nasal polyps by targeting ZEB1 via ERK/p38 pathway

Sun

et al. 2023

Int Forum Allergy Rhinol

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BackgroundSeveral biological processes are regulated by miR‐200a‐3p, including cell proliferation, migration, and epithelial–mesenchymal transition (EMT). In this study we aimed to uncover the diagnostic value and molecular mechanisms of miR‐200a‐3p in chronic rhinosinusitis with nasal polyps (CRSwNP).MethodsThe expressions of miR‐200a‐3p were detected by quantitative real‐time polymerase chain reaction (qRT‐PCR), Zinc finger E‐box binding homeobox 1 (ZEB1) levels were examined by qRT‐PCR and immunofluorescence staining. The interaction between miR‐200a‐3p and ZEB1 was predicted by TargetScan Human 8.0 and confirmed by dual‐luciferase reporter assays. In addition, the effect of miR‐200a‐3p and ZEB1 on EMT‐related makers and inflammation cytokines was assessed by qRT‐PCR and Western blotting in human nasal epithelial cells (hNEpCs) and primary human nasal mucosal epithelial cells (hNECs).ResultsWe found that miR‐200a‐3p was downregulated in non‐eosinophilic and eosinophilic CRSwNP patients when compared with controls. The diagnostic value of miR‐200a‐3p in serum is reflected by the receiver operating characteristic curve and the 22‐item Sino‐Nasal Outcome Test. Bioinformatic analysis and luciferase reporter assay identified ZEB1 as a target of miR‐200a‐3p. ZEB1 was more highly expressed in CRSwNP than in controls. Furthermore, miR‐200a‐3p inhibitor or ZEB1 overexpression significantly suppressed the epithelial marker E‐cadherin; promoted the activation of vimentin, α‐spinal muscle atrophy, and N‐cadherin; and aggravated inflammation in hNEpCs. Knockdown of ZEB1 significantly alleviated the cellular remodeling caused by miR‐200a‐3p inhibitor via the extracellular signal‐regulated kinase (ERK)/p38 pathway in hNECs.ConclusionsmiR‐200a‐3p suppresses EMT and inflammation by regulating the expression of ZEB1 via the ERK/p38 pathway. Our study presents new ideas for protecting nasal epithelial cells from tissue remodeling and finding a possible target for disease.

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Sirtuin 1 attenuates nasal polypogenesis by suppressing epithelial-to-mesenchymal transition

Cited by 63 publications

References 43 publications

Sinonasal Delivery of Resveratrol via Mucoadhesive Nanostructured Microparticles in a Nasal Polyp Mouse Model

Sinonasal Delivery of Resveratrol via Mucoadhesive Nanostructured Microparticles in a Nasal Polyp Mouse Model

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

miR‐200a‐3p regulates epithelial–mesenchymal transition and inflammation in chronic rhinosinusitis with nasal polyps by targeting ZEB1 via ERK/p38 pathway

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