Clinical Department of Otorhinolaryngology, Head and Neck Surgery University Hospital Osijek, HR-31000 Osijek, Croatia.
Department of Otorhinolaryngology, Maxillofacial Surgery Faculty of Medicine University of Osijek, HR-31000 Osijek, Croatia.
Int J Mol Sci. 2022 May 15;23(10):5521. doi: 10.3390/ijms23105521.
Chronic rhinosinusitis (CRS) is a prevalent, multifaceted inflammatory condition affecting the nasal cavity and the paranasal sinuses, frequently accompanied by formation of nasal polyps (CRSwNP). This apparently uniform clinical entity is preceded by heterogeneous changes in cellular and molecular patterns, suggesting the presence of multiple CRS endotypes and a diverse etiology. Alterations of the upper airway innate defense mechanisms, including antimicrobial and antioxidant capacity, have been implicated in CRSwNP etiology. The aim of this study was to investigate mRNA expression patterns of antioxidative enzymes, including superoxide dismutase (SOD) and peroxiredoxin-2 (PRDX2), and innate immune system defense players, namely the bactericidal/permeability-increasing fold-containing family A, member 1 (BPIFA1) and PACAP family members, particularly adenylate-cyclase-activating polypeptide receptor 1 (ADCYAP1) in nasal mucosa and nasal polyps from CRSwNP patients. Additional stratification based on age, sex, allergic comorbidity, and disease severity was applied. The results showed that ADCYAP1, BPIFA1, and PRDX2 transcripts are differentially expressed in nasal mucosa and scale with radiologically assessed disease severity in CRSwNP patients. Sinonasal transcriptome is not associated with age, sex, and smoking in CRSwNP. Surgical and postoperative corticosteroid (CS) therapy improves endoscopic appearance of the mucosa, but variably reverses target gene expression patterns in the nasal cavity of CRSwNP patients. Transcriptional cross-correlations analysis revealed an increased level of connectedness among differentially expressed genes under inflammatory conditions and restoration of basic network following CS treatment. Although results of the present study imply a possible engagement of ADCYAP1 and BPIFA1 as biomarkers for CRSwNP, a more profound study taking into account disease severity and CRSwNP endotypes prior to the treatment would provide additional information on their sensitivity.
慢性鼻-鼻窦炎(CRS)是一种普遍存在的、多方面的炎症性疾病,影响鼻腔和鼻窦,常伴有鼻息肉(CRSwNP)形成。这种明显统一的临床实体之前存在细胞和分子模式的异质性变化,表明存在多种 CRS 表型和不同的病因。上呼吸道先天防御机制的改变,包括抗菌和抗氧化能力,与 CRSwNP 的病因有关。本研究旨在研究抗氧化酶,包括超氧化物歧化酶(SOD)和过氧化物还原酶-2(PRDX2),以及先天免疫系统防御因子的 mRNA 表达模式,即杀菌/通透性增加的折叠含家族 A,成员 1(BPIFA1)和 PACAP 家族成员,特别是腺苷酸环化酶激活多肽受体 1(ADCYAP1)在 CRSwNP 患者的鼻黏膜和鼻息肉中的表达。根据年龄、性别、过敏合并症和疾病严重程度进行了额外的分层。结果表明,ADCYAP1、BPIFA1 和 PRDX2 转录本在 CRSwNP 患者的鼻黏膜和鼻腔中均有差异表达,并与放射学评估的疾病严重程度相关。鼻转录组与 CRSwNP 患者的年龄、性别和吸烟无关。鼻息肉切除术和术后皮质类固醇(CS)治疗改善了黏膜的内镜外观,但在 CRSwNP 患者的鼻腔中,不同程度地逆转了靶基因表达模式。转录交叉相关分析显示,在炎症条件下差异表达基因之间的连接水平增加,在 CS 治疗后基本网络得到恢复。尽管本研究的结果表明,ADCYAP1 和 BPIFA1 可能作为 CRSwNP 的生物标志物,但在治疗前考虑疾病严重程度和 CRSwNP 表型,进行更深入的研究将提供有关其敏感性的更多信息。