Mucus composition abnormalities in sinonasal mucosa of chronic rhinosinusitis with and without nasal polyps

Mucus composition abnormalities in sinonasal mucosa of chronic rhinosinusitis with and without nasal polyps
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伴有或不伴有鼻息肉的慢性鼻窦炎鼻窦粘膜粘液成分异常

DOI:
10.1007/s10753-021-01471-6
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发表时间:
2021-05-17
期刊:
影响因子:
5.1
通讯作者:
Wang, De-Yun
Wang, De-Yun
中科院分区:
医学2区
文献类型:
--
作者:
Tu, Yanyi;Liu, Jing;Wang, De-Yun

文献摘要

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黏液分泌及其组成对维持呼吸道健康至关重要,其中低氧诱导因子(HIF)被认为参与黏蛋白合成和调节的调节。健康人和慢性鼻-鼻窦炎(CRS)患者鼻腔粘液成分的差异可能是慢性鼻部疾病的发病机制之一,但到目前为止,它们的作用尚未完全清楚。鼻活检标本取自24例健康人和99例CRS患者,其中36例为CRSsNP,63例为CRSwNP。采用免疫组织化学(IHC)和免疫荧光(IF)染色、实时定量聚合酶链式反应(RT-PCR)和免疫印迹法(Western印迹)比较两组受试者鼻腔粘液成分。CRSsNP患者浆液腺和粘液腺面积均明显增大。在CRSwNP患者中,观察到粘膜下腺密度降低和杯状细胞显著增加。CRSsNP和CRSwNP鼻腔粘膜中形成凝胶的主要粘蛋白分别为MUC5B和MUC5AC。粘液细胞在CRSsNP和CRSwNP中所占比例较高。CRSwNP组MUC5AC阳性杯状细胞比例增加。CRS组织中HIF-2α的表达水平显著升高,且HIF-1α和HIF-2α在浆液细胞中均有表达,而在粘液细胞中无表达。CRS鼻腔粘膜粘液过度分泌,粘液成分改变,主要与CRSsNP的腺体增生和CRSwNP的杯状细胞增生有关。粘液的异常损害了鼻腔粘膜的非特异性和特异性的抗菌能力。HIF的表达可能与粘蛋白合成和浆液腺调节的差异有关,这需要进一步研究以了解CRS的病理机制。
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.