Department of Otolaryngology-Head and Neck Surgery, Shandong Provincial ENT Hospital Affiliated to Shandong University, No. 4 Duanxing West Road, Jinan, 250000, Shandong, China.
Department of Otolaryngology, Yong Loo Lin School of Medicine, National University of Singapore, 1E Kent Ridge Rd, Singapore, 119228, Singapore.
Inflammation. 2021 Oct;44(5):1937-1948. doi: 10.1007/s10753-021-01471-6. Epub 2021 May 17.
Mucus secretion and its composition are vital in the maintenance of airway health, among which hypoxia-inducible factors (HIFs) are thought to be involved in the regulation of mucin synthesis and regulation. Nasal mucus composition difference between healthy individuals and chronic rhinosinusitis (CRS) patients may contribute to the pathology of chronic nasal diseases, but so far, their role has yet to be completely understood. Nasal biopsy specimens were obtained from 24 healthy subjects and 99 patients with CRS without (CRSsNP, n=36) or with (CRSwNP, n=63) nasal polyps. Immunohistochemical (IHC) and immunofluorescent (IF) staining, quantitative real-time PCR, and western blot were performed to compare the nasal mucus composition between the subjects. Areas of the serous gland and mucous gland were both significantly increased in CRSsNP patients. In CRSwNP patients, a decrease in submucosal gland density and a marked increase in goblet cells were observed. The major gel-forming mucins in the sinonasal mucosa of CRSsNP and CRSwNP are MUC5B and MUC5AC respectively. Mucous cells are found in a higher proportion in both CRSsNP and CRSwNP. The proportion of MUC5AC-positive goblet cells was increased in CRSwNP. The mRNA level of HIF-2α was significantly increased in CRS, and both HIF-1α and HIF-2α were expressed in serous cell but not mucous cell. Over secretion and altered composition of mucus are observed in sinonasal mucosa of CRS, which was mainly associated with glandular hyperplasia in CRSsNP and goblet cell hyperplasia in CRSwNP. Mucus abnormality compromised both non-specific and specific antimicrobial capabilities in the sinonasal mucosa. HIF expression may contribute to differences in mucin synthesis and serous gland regulation, which needs further investigation to understand the pathology of CRS.
黏液分泌及其成分对于气道健康至关重要，其中缺氧诱导因子（HIFs）被认为参与调节黏蛋白的合成和调控。健康个体和慢性鼻-鼻窦炎（CRS）患者的鼻黏液成分的差异可能导致慢性鼻疾病的发生，但迄今为止，其作用尚未完全阐明。本研究从 24 名健康受试者和 99 名 CRS 患者（无鼻息肉的 CRSsNP，n=36；有鼻息肉的 CRSwNP，n=63）中获得鼻活检标本。通过免疫组织化学（IHC）和免疫荧光（IF）染色、实时定量 PCR 和 Western blot 比较了受试者的鼻黏液成分。CRSsNP 患者的浆液腺和黏液腺面积均显著增加。在 CRSwNP 患者中，观察到黏膜下腺密度降低和杯状细胞明显增加。CRSsNP 和 CRSwNP 患者的鼻窦黏膜中主要的凝胶形成黏蛋白分别是 MUC5B 和 MUC5AC。在 CRSsNP 和 CRSwNP 中均发现黏液细胞比例较高。CRSwNP 中 MUC5AC 阳性杯状细胞的比例增加。CRS 中 HIF-2α 的 mRNA 水平显著增加，HIF-1α 和 HIF-2α 均在浆液细胞中表达，但不在黏液细胞中表达。CRS 中观察到鼻黏膜黏液过度分泌和组成改变，这主要与 CRSsNP 中的腺体增生和 CRSwNP 中的杯状细胞增生有关。黏液异常损害了鼻黏膜的非特异性和特异性抗菌能力。HIF 表达可能有助于黏蛋白合成和浆液腺调节的差异，需要进一步研究以了解 CRS 的病理生理学。
