Expression of Matrix Metalloproteinases and Their Tissue Inhibitors in Chronic Rhinosinusitis With Nasal Polyps: Etiopathogenesis and Recurrence

Guerra, Germano; Testa, Domenico; Salzano, Francesco Antonio; Tafuri, Domenico; Hay, Eleonora; Bs, Antonetta Schettino; Iovine, R; Marcuccio, Giuseppina; Motta, Giovanni

doi:10.1177/0145561319896635

Cited by 10 publications

(6 citation statements)

References 32 publications

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“…Downregulated CRS genes were physical-barrier protein genes of the calcium-binding protein A7 S100A7 family and the matrix metallopeptidase 9 MMP9 , extensively related to barrier defects in both phenotypes of the CRS [ 49 , 50 ]. Transmembrane proteinase TMPRSS11B has been detected in various tissues, including the airways, but its function remains undetermined [ 51 ].…”

Section: Discussionmentioning

confidence: 99%

Transcriptomic Differentiation of Phenotypes in Chronic Rhinosinusitis and Its Implications for Understanding the Underlying Mechanisms

Urbančič

Soklič

Luzar

et al. 2023

IJMS

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Chronic rhinosinusitis (CRS) is a multifaceted disease with variable clinical courses and outcomes. We aimed to determine CRS-associated nasal-tissue transcriptome in clinically well-characterized and phenotyped individuals, to gain a novel insight into the biological pathways of the disease. RNA-sequencing of tissue samples of patients with CRS with polyps (CRSwNP), without polyps (CRSsNP), and controls were performed. Characterization of differently expressed genes (DEGs) and functional and pathway analysis was undertaken. We identified 782 common CRS-associated nasal-tissue DEGs, while 375 and 328 DEGs were CRSwNP- and CRSsNP-specific, respectively. Common key DEGs were found to be involved in dendritic cell maturation, the neuroinflammation pathway, and the inhibition of the matrix metalloproteinases. Distinct CRSwNP-specific DEGs were involved in NF-kβ canonical pathways, Toll-like receptor signaling, HIF1α regulation, and the Th2 pathway. CRSsNP involved the NFAT pathway and changes in the calcium pathway. Our findings offer new insights into the common and distinct molecular mechanisms underlying CRSwNP and CRSsNP, providing further understanding of the complex pathophysiology of the CRS, with future research directions for novel treatment strategies.

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Section: Discussionmentioning

confidence: 99%

Transcriptomic Differentiation of Phenotypes in Chronic Rhinosinusitis and Its Implications for Understanding the Underlying Mechanisms

Urbančič

Soklič

Luzar

et al. 2023

IJMS

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“…It is commonly known that MMPs are likely to be associated with airway remodeling in CRSwNPs based on the increased expression of MMP-2 and MMP-9 in patients with CRSwNPs compared with control subjects ( 36 - 38 ). Numerous studies have found that the levels of MMPs are significantly increased in CRSwNPs compared with healthy control tissues and that the levels of TIMPs are significantly decreased ( 10 - 13 ). In the present study, no healthy samples were analyzed as a control group, so it cannot be concluded that the expression levels of MMP-2, MMP-9, TIMP-1 and miR-29b-3p differ in CRSwNPs compared with healthy individuals.…”

Section: Discussionmentioning

confidence: 99%

“…In addition, MMPs are regulated by a variety of biological processes, including transcription and posttranscription processes, and their main regulators are tissue inhibitors of matrix metalloproteinases (TIMPs) ( 9 ). Numerous studies have found that MMPs and TIMPs are specifically expressed in chronic rhinosinusitis with nasal polyps (CRSwNPs); for example, the levels of MMP-2 and MMP-9 are significantly increased in CRSwNPs, and the levels of TIMP-1 and TIMP-4 are significantly decreased ( 10 - 13 ). In addition, corticosteroids and budesonide contribute to ameliorating inflammation by downregulating the expression of MMP-2 and MMP-9 ( 14 ) and upregulating the levels of TIMP-1, TIMP-2 and TIMP-4 ( 15 ).…”

Section: Introductionmentioning

confidence: 99%

Downregulation of miR‑29b‑3p promotes α‑tubulin deacetylation by targeting the interaction of matrix metalloproteinase‑9 with integrin β1 in nasal polyps

Liu

et al. 2021

Int J Mol Med

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Matrix metalloproteinase (MMP)-9 is a key enzyme responsible for extracellular matrix degradation and contributes to the progressive histological changes observed in lower respiratory tract infections. Integrin β1 and α-tubulin are potential MMP-9-interacting proteins, and microRNA (miR)-29b-3p can regulate MMP-9 expression. MMP-9 is highly expressed in chronic rhinosinusitis with nasal polyps (cRSwNPs), regardless of its effects on miR-29b-3p, integrin β1 and α-tubulin expression. In the present study, samples from 100 patients with cRSwNPs were examined via reverse transcription-quantitative PcR to assess the mRNA expression of miR-29b-3p, and western blotting was performed to assess the protein expression of MMP-2, MMP-9, acetyl-α-tubulin, integrin β1 and tissue inhibitor of metalloproteinase 1 (TIMP-1). A dual-luciferase reporter assay was used to verify the direct binding of miR-29b-3p and MMP-2/MMP-9. co-immunoprecipitation (co-IP) and GST pull-down assays showed that integrin β1 and α-tubulin were MMP-9-interacting proteins. Cell viability, apoptosis and inflammatory cytokine levels were determined via a Cell Counting Kit-8 assay, flow cytometry and ELISA, respectively. miR-29b-3p expression was found to be positively correlated with MMP-2 and MMP-9 expression. Whereas, TIMP-1 expression was negatively correlated with MMP-2 and MMP-9 expression. The dual-luciferase assay revealed that miR-29b-3p targeted the 3' untranslated region of MMP-2/MMP-9. The co-IP and GST pull-down assays showed that MMP-9 could directly bind to integrin β1 and indirectly bind to α-tubulin. Finally, the overexpression of miR-29b-3p decreased the expression of MMP-9 and increased the levels of acetyl-α-tubulin. By contrast, the knockdown of miR-29b-3p increased the expression of MMP-9 and decreased the levels of acetyl-α-tubulin. Additionally, MMP-9 expression was found to be negatively correlated with acetyl-α-tubulin expression. Of note, the expression of integrin β1 did not change following the overexpression and knockdown of MMP-9. Finally, the overexpression of miR-29b-3p not only decreased MMP-9 expression, but also alleviated lipopolysaccharide-induced inflammation in NP69 cells. The results showed that the downregulation of miR-29b-3p promoted α-tubulin deacetylation by increasing the number of MMP-9-integrin β1 complexes in cRSwNPs, thus targeting miR-29b-3p/MMP-9 may be a potential novel strategy for the clinical treatment of cRSwNPs.

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“…A plethora of studies already investigated the role of MMPs and TIMPs in the etiopathogenesis of nasal polyps in CRSwNP. Multiple types of MMPs have been studied but the most common ones associated with CRSwNP are MMPs -2, -7 and -9 [55].…”

Section:  the Involvement Of The Matrix Metalloproteinases (Mmps) Inmentioning

confidence: 99%

Latest advances in chronic rhinosinusitis with nasal polyps endotyping and biomarkers, and their significance for daily practice

Maniu

Perde-Schrepler

Tatomir

et al. 2020

Rom J Morphol Embryol

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The term chronic rhinosinusitis (CRS) comprises of an assortment of diseases that share a common feature: inflammation of the sinonasal mucosa. The phenotype classification of CRS, based on the presence of polyps, has failed to offer a curative treatment for the disease, particularly in refractory cases. Chronic rhinosinusitis with nasal polyps (CRSwNP) remains a challenging entity. Researchers have made efforts trying to characterize subtypes of the disease according to the endotypes, which are delineated by different immunological pathways, using biomarkers. Even if the inflammatory processes controlling CRSwNP are not fully understood, data suggested that the disease associated with a type 2 inflammatory mechanisms can be also linked to the type 1 or type 3 pathomechanism, being highly heterogeneous. Biomarkers for CRSwNP are proposed, such as: eosinophil count, cytokines, metalloproteinases, bitter and sweet taste receptors, and the nasal microbiome. For endotyping to be clinically applicable and simply determined, biomarkers referring to the intrinsic biomolecular mechanism still need to be found. Precision medicine is becoming the new standard of care, but innovative therapies such as biologics may be rather challenging for the clinicians in their daily practice. This new approach to CRSwNP implies patient selection and a simple algorithm for deciding the right treatment, easy to implement and adjust. Our review points out the ongoing new research on the pathophysiology of CRSwNP, biomarkers and treatment opportunities. It allows clinicians to keep abreast of current evidence-based knowledge and to individualize the management of CRSwNP, especially in refractory cases.

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Expression of Matrix Metalloproteinases and Their Tissue Inhibitors in Chronic Rhinosinusitis With Nasal Polyps: Etiopathogenesis and Recurrence

Cited by 10 publications

References 32 publications

Transcriptomic Differentiation of Phenotypes in Chronic Rhinosinusitis and Its Implications for Understanding the Underlying Mechanisms

Transcriptomic Differentiation of Phenotypes in Chronic Rhinosinusitis and Its Implications for Understanding the Underlying Mechanisms

Downregulation of miR‑29b‑3p promotes α‑tubulin deacetylation by targeting the interaction of matrix metalloproteinase‑9 with integrin β1 in nasal polyps

Latest advances in chronic rhinosinusitis with nasal polyps endotyping and biomarkers, and their significance for daily practice

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