The development of nasal polyps involves early middle meatus mucous remodeling via TGF-β1 mediated PAI-1 reduction

Brazilian Journal of Otorhinolaryngology

Available online 14 February 2023

Brazilian Journal of OtorhinolaryngologyAuthor links open overlay panel, , , , , , Highlights•

We have investigated the fibrosis genes in the TGF-β pathway in the early and mature nasal polyps development process, respectively.

PAI-1 is involved in early nasal polyps, and its low fibrolysis is predisposed to nasal polyps’ development, which provides new insight into its clinical intervention.

PAI-1 is affected by the TGF pathway, and low PAI-1 expression is one of the main reasons for tissue remodeling in nasal polyps.

AbstractObjective

Our study aimed to elucidate the effect of PAI-1 (Plasminogen Activator Inhibitor-1) and t-PA (Tissue-type Plasminogen Activator) in tissue remodeling in nasal polyps patients.

Methods

Samples were streamed as early Nasal Polyps (eNP, n = 10) and inferior tissue from the same patient, mature Nasal Polyps (mNP, n = 14), and Control group (n = 15), respectively. Immunohistochemistry and immunofluorescence were applied to detect localization. Quantitative Real-Time Polymerase Chain Reaction (qRT-PCR) and Western blot were used to measure different levels among three groups. The mNP tissue was cultured in vitro and treated with TGF-β1 (Transforming Growth Factor-beta 1) activator, TGF-β1 inhibitor (SB431542), and PAI-1 inhibitor (TM5275); then Western blot, qRT-PCR, and ELISA were used to assess changes.

Results

The immunohistochemistry and immunofluorescence showed that PAI-1 expression decreased in eNP and mNP, mainly in epithelium and glands. The transcriptional expression and protein level of TGF-β1/t-PA/PAI-1/Collagen1 were lower in eNP than IT while mNP group demonstrated lower mRNA expression and protein level of TGF-β1/t-PA/PAI-1/Collagen1 than Control group. In mNP tissue culture in vitro, TGF-β1 activator elevated t-PA, PAI-1, and Collagen1 with higher release of PAI-1 and Collagen1 in supernatant, whereas SB431542 suppressed above reactions; TM5275 lowered transcriptional and protein level of Collagen1 in supernatant.

Conclusion

Early Nasal polyps’ formation in middle meatus mucous is related with fibrillation system PAI-1/t-PA and tissue remodeling; moreover, nasal polyps’ development is regulated by TGF-β1-mediated PAI-1 reduction.

Keywords

Tissue remodeling

Fibrosis

Early nasal polyps

TGF-β1

Tissue culture in vitro

© 2023 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier España, S.L.U.

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