Differential Expression of Extracellular Matrix Components in Nasal Polyp Endotypes

Differential Expression of Extracellular Matrix Components in Nasal Polyp Endotypes
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鼻息肉内型细胞外基质成分的差异表达

DOI:
10.1177/1945892419860634
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发表时间:
2019-11-01
影响因子:
2.6
通讯作者:
Steinke, John W.
Steinke, John W.
中科院分区:
医学3区
文献类型:
--
作者:
Feng, Xin;Payne, Spencer C.;Steinke, John W.

文献摘要

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背景慢性鼻窦炎是一种难治性疾病,其特点是手术切除后复发的鼻息肉(NP)。根据细胞浸润性或潜在的生理机制,该病已被分为不同的表型。NPS由炎性细胞浸润、血管和大量细胞外基质(ECM)组成。尽管人们认识到显著的细胞外基质沉积,但很少有研究详细检查这些成分以及它们与疾病状态的差异。目的定量检测细胞外基质成分在神经细胞中的表达。方法用微天狼星红染色检测纳米粒的总胶原含量,免疫荧光法检测I型胶原、III型胶原、IV型胶原、纤维连接蛋白和层粘连蛋白。定量分析每种基因的表达与鼻窦炎表型的关系,并分别作为息肉嗜酸粒细胞数量的函数。结果按表型分析,I型胶原、III型胶原和纤维连接蛋白在非嗜酸性鼻窦疾病中的表达水平最高。IV型胶原蛋白在任何组中都没有不同,其位置主要在血管周围。当分析为息肉嗜酸粒细胞数量的函数时,总胶原蛋白和III型胶原蛋白显示出显著的负相关。结论NP ECM的组成因病情不同而不同,在嗜酸性粒细胞水平低的病例中有较高的表达。这表明在嗜酸性息肉中,有基质沉积的损失,要么是由于分解,要么是因为无法产生必要的成分。了解这些差异可能会确定新的治疗靶点。
Background Chronic rhinosinusitis is a difficult-to-treat disease that is often characterized by recurrent nasal polyp (NP) growth following surgical removal. The disease has been separated into distinct phenotypes based on cellular infiltrate or underlying physiological mechanisms. NPs are composed in part of an inflammatory cellular infiltrate, blood vessels, and a large amount of extracellular matrix (ECM). Despite the recognition of prominent ECM deposition, few studies have examined the components in detail and how they might differ with disease state. Objective The purpose of this study was to quantitate the expression of ECM components in NPs. Methods NPs were stained with pico-sirius red to determine total collagen content, and immunofluorescence was used to detect collagen I, collagen III, collagen IV, fibronectin, and laminin. Expression of each was quantitated and analyzed in relation to rhinosinusitis phenotype and separately as a function of polyp eosinophil number. Results When analyzed by phenotype, collagen I, collagen III, and fibronectin were expressed at the highest levels in noneosinophilic sinus disease. Collagen IV was not different among any groups, and its location was found predominately around vessels. When analyzed as a function of polyp eosinophil number, total collagen and collagen III showed a significant inverse correlation. Conclusions NP ECM composition differs with disease state with higher expression in cases where eosinophil levels are low. This suggests that in eosinophilic polyps there is a loss of matrix deposition either through break down or a failure to produce the essential components. Understanding these differences may identify new therapeutic targets.