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慢性鼻-鼻窦炎伴鼻息肉(CRSwNP)和不伴鼻息肉(CRSsNP)患者鼻窦上皮组织中CNPase及TGFβ1/Smad信号通路分子表达的评估

Evaluation of CNPase and TGFβ1/Smad Signalling Pathway Molecule Expression in Sinus Epithelial Tissues of Patients with Chronic Rhinosinusitis with (CRSwNP) and without Nasal Polyps (CRSsNP).

作者信息

Piszczatowska Katarzyna, Czerwaty Katarzyna, Dżaman Karolina, Jermakow Natalia, Brzost Jacek, Kantor Ireneusz, Ludwig Nils, Szczepański Mirosław J

机构信息

Department of Biochemistry, Medical University of Warsaw, 02-091 Warsaw, Poland.

Department of Otolaryngology, The Medical Centre of Postgraduate Education, 01-813 Warsaw, Poland.

出版信息

J Pers Med. 2024 Aug 23;14(9):894. doi: 10.3390/jpm14090894.

Abstract

Chronic rhinosinusitis with and without nasal polyps (CRSwNP and CRSsNP, respectively) is a chronic inflammatory disease affecting almost 5 to 12% of the population and exhibiting high recurrence rates after functional endoscopic sinus surgery (FESS). TGFβ1-related pathways contribute to tissue remodelling, which is one of the key aspects of CRS pathogenesis. Additionally, adenosine signalling participates in inflammatory processes, and CNPase was shown to elevate adenosine levels by metabolizing cyclic monophosphates. Thus, the aim of this study was to assess the expression levels of Smad2, pSmad3, TGFβ1, and CNPase protein via immunohistochemistry in sinus epithelial tissues from patients with CRSwNP ( = 20), CRSsNP ( = 23), and non-CRS patients ( = 8). The expression of Smad2, pSmad3, TGFβ1, and CNPase was observed in the sinus epithelium and subepithelial area of all three groups of patients, and their expression correlated with several clinical symptoms of CRS. Smad2 expression was increased in CRSsNP patients compared to CRSwNP patients and controls ( = 0.001 and < 0.001, respectively), pSmad3 expression was elevated in CRSwNP patients compared to controls ( = 0.007), TGFβ1 expression was elevated in CRSwNP patients compared to controls ( = 0.009), and CNPase was decreased in CRSsNP patients compared to controls ( = 0.03). To the best of our knowledge, we are the first to demonstrate CNPase expression in the upper airway epithelium of CRSwNP, CRSsNP, and non-CRS patients and point out a putative synergy between CNPase and TGFβ1/Smad signalling in CRS pathogenesis that emerges as a novel still undiscovered aspect of CRS pathogenesis; further studies are needed to explore its function in the course of the chronic inflammation of the upper airways.

摘要

伴鼻息肉和不伴鼻息肉的慢性鼻-鼻窦炎(分别为CRSwNP和CRSsNP)是一种慢性炎症性疾病,影响着近5%至12%的人群,并且在功能性鼻内镜鼻窦手术(FESS)后复发率很高。转化生长因子β1(TGFβ1)相关通路有助于组织重塑,这是CRS发病机制的关键方面之一。此外,腺苷信号传导参与炎症过程,并且已表明2',3'-环核苷酸3'-磷酸二酯酶(CNPase)通过代谢环磷酸酯来提高腺苷水平。因此,本研究的目的是通过免疫组织化学评估CRSwNP患者(n = 20)、CRSsNP患者(n = 23)和非CRS患者(n = 8)鼻窦上皮组织中Smad2、磷酸化Smad3(pSmad3)、TGFβ1和CNPase蛋白的表达水平。在所有三组患者的鼻窦上皮和上皮下区域均观察到Smad2、pSmad3、TGFβ1和CNPase的表达,并且它们的表达与CRS的几种临床症状相关。与CRSwNP患者和对照组相比,CRSsNP患者中Smad2表达增加(分别为P = 0.001和P < 0.001),与对照组相比,CRSwNP患者中pSmad3表达升高(P = 0.007),与对照组相比,CRSwNP患者中TGFβ1表达升高(P = 0.009),与对照组相比,CRSsNP患者中CNPase降低(P = 0.03)。据我们所知,我们是首个证明CNPase在CRSwNP、CRSsNP和非CRS患者上呼吸道上皮中的表达,并指出CNPase与TGFβ1/Smad信号传导在CRS发病机制中存在潜在协同作用的研究,这是CRS发病机制中一个尚未被发现的新方面;需要进一步研究以探索其在上呼吸道慢性炎症过程中的作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bcad/11433593/a242e08bdff6/jpm-14-00894-g006.jpg

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