鼻息肉的发展涉及通过 TGF-β1 介导的 PAI-1 减少导致的早期中鼻道黏膜重塑。

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

机构信息

The First Affiliated Hospital of Chongqing Medical University, Department of Otorhinolaryngology, Chongqing, China.

出版信息

Braz J Otorhinolaryngol. 2023 May-Jun;89(3):366-373. doi: 10.1016/j.bjorl.2023.01.007. Epub 2023 Feb 14.

DOI:10.1016/j.bjorl.2023.01.007

PMID:36841712

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10164765/

Abstract

OBJECTIVE

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.

LEVEL OF EVIDENCE

3b.

摘要

目的

本研究旨在阐明 PAI-1（纤溶酶原激活物抑制剂-1）和 t-PA（组织型纤溶酶原激活物）在鼻息肉患者组织重塑中的作用。

方法

分别采集早期鼻息肉（eNP，n=10）和同一患者下鼻甲组织、成熟鼻息肉（mNP，n=14）及对照组（n=15）的样本。应用免疫组化和免疫荧光检测定位。采用实时定量聚合酶链反应（qRT-PCR）和 Western blot 检测三组间不同水平。体外培养 mNP 组织，用 TGF-β1 激活剂、TGF-β1 抑制剂（SB431542）和 PAI-1 抑制剂（TM5275）处理，然后用 Western blot、qRT-PCR 和 ELISA 评估变化。

结果

免疫组化和免疫荧光显示，eNP 和 mNP 中 PAI-1 表达减少，主要位于上皮和腺体。eNP 组中 TGF-β1/t-PA/PAI-1/胶原 1 的转录表达和蛋白水平均低于 IT 组，而 mNP 组 TGF-β1/t-PA/PAI-1/胶原 1 的 mRNA 表达和蛋白水平均低于对照组。体外 mNP 组织培养中，TGF-β1 激活剂升高 t-PA、PAI-1 和胶原 1，上清液中 PAI-1 和胶原 1 释放增加，而 SB431542 抑制上述反应；TM5275 降低上清液中胶原 1 的转录和蛋白水平。