Evidence for role of acid-sensing ion channel 1a in chronic rhinosinusitis with nasal polyps
Evidence for role of acid-sensing ion channel 1a in chronic rhinosinusitis with nasal polyps
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酸敏感离子通道 1a 在伴有鼻息肉的慢性鼻窦炎中作用的证据
DOI：
10.1007/s00405-020-06521-7
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发表时间：
2021-01
影响因子：
2.6
通讯作者：
Weitian Zhang
中科院分区：
文献类型：
--
作者：
Ru Tang;Guangyi Ba;Mingxian Li;Zhipeng Li;Haibo Ye;Hai Lin;Weitian Zhang
目的慢性鼻窦炎伴鼻息肉（CRSwNP）患者鼻黏膜组织中多种炎症细胞浸润，尤其是哮喘患者。酸敏感离子通道1a （ASIC1a）在感知酸化和触发炎症的过程中至关重要。然而，其在CRSwNP中的作用和机制尚不清楚。本研究旨在探讨ASIC1a在CRSwNP发病机制中的作用和机制。方法收集对照组、伴有或不伴有哮喘的CRSwNP患者的鼻腔分泌物，测定其pH值。采用Western blotting、real-time PCR和免疫组化（IHC）技术评估ASIC1a在纳入研究对象鼻组织样本中的表达。免疫荧光染色评价ASIC1a与炎性细胞的共定位。然后，分散的鼻息肉细胞（DNPCs）在酸化条件下（pH 6.0）培养，加或不加ASIC1a抑制剂阿米洛胺。采用Western blotting、real-time PCR、LDH活性试剂盒、ELISA检测刺激剂对细胞的作用及机制。结果CRSwNP合并哮喘患者鼻分泌物pH值明显降低。在哮喘CRSwNP患者中发现ASIC1a蛋白、mRNA水平和阳性细胞显著上调。在多种炎症细胞中检测到ASIC1a。在培养的DNPCs中，在酸化条件下（pH 6.0）发现ASIC1a水平，LDH活性，HIF-1α水平和炎症细胞因子的显著改变，但阿米洛利可以阻止。结论ASIC1a基因的上调可能在CRSwNP，尤其是哮喘CRSwNP发病过程中，通过增强HIF-1α表达和LDH活性激活炎症细胞，感知酸化并引发炎症反应的过程中起重要作用。
PurposeA variety of inflammatory cells are infiltrated histologically in sinonasal mucosa of chronic rhinosinusitis with nasal polyps (CRSwNP), especially CRSwNP with asthma. Acid-sensing ion channel 1a (ASIC1a) is essential in the process of sensing acidification and triggering inflammation. Whereas, its role and mechanism in CRSwNP remain uncertain. The present study aimed to explore the roles and mechanism of ASIC1a in the pathogenesis of CRSwNP.MethodsNasal secretions from control subjects, patients with CRSwNP with or without asthma were collected for measuring pH values. Western blotting, real-time PCR and immunohistochemistry (IHC) were employed to assess ASIC1a expression in nasal tissue samples from included subjects. The co-localization of ASIC1a with inflammatory cells was evaluated by immunofluorescence staining. Then, dispersed nasal polyp cells (DNPCs) were cultured under acidified condition (pH 6.0), with or without ASIC1a inhibitor amiloride. Western blotting, real-time PCR, LDH activity kit, and ELISA were performed to assess the effects and mechanisms of stimulators on the cells.ResultsThe pH values were significantly lower in the nasal secretions from patients with CRSwNP with asthma. Significant upregulation of ASIC1a protein, mRNA levels, and positive cells was found in CRSwNP with asthma. ASIC1a was detected in a variety of inflammatory cells. In cultured DNPCs, significant alterations of ASIC1a levels, LDH activity, HIF-1α levels, and inflammatory cytokines were found under acidified condition (pH 6.0), but were prevented by amiloride.ConclusionUpregulation of ASIC1a might be essential in the process of sensing acidification and triggering inflammatory response via enhancing HIF-1α expression and LDH activity to activate inflammatory cells in the pathogenesis of CRSwNP, especially in CRSwNP with asthma.
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影响因子：
2.3
作者：
Crisafulli E;Barbeta E;Ielpo A;Torres A
通讯作者：
Torres A
DOI：
10.1007/s00359-019-01365-x
发表时间：
2019-08
期刊：
Journal of Comparative Physiology A
影响因子：
--
作者：
Z. Çakır;Caner Yildirim;İlay Buran;Ebru Önalan;R. Bal
通讯作者：
Z. Çakır;Caner Yildirim;İlay Buran;Ebru Önalan;R. Bal
影响因子：
6.4
作者：
Cho, Do-Yeon;Hwang, Peter H.;Illek, Beate;Fischer, Horst
通讯作者：
Fischer, Horst
影响因子：
7.2
作者：
Fokkens, Wytske J.;Lund, Valerie J.;Wormald, Peter John
通讯作者：
Wormald, Peter John
影响因子：
4.6
作者：
Ortega-Ramírez A;Vega R;Soto E
通讯作者：
Soto E