Lin Hai, Lin Dong, Xiong Xi-Sheng, Dai Xiong-Xiong, Lin Ting
Department of Otorhinolaryngology, Eye and ENT Hospital of Fudan University, Shanghai, China; Department of Otorhinolaryngology, Fuzhou General Hospital, Fuzhou, Fujian, China.
Int Forum Allergy Rhinol. 2014 Nov;4(11):909-14. doi: 10.1002/alr.21419. Epub 2014 Sep 25.
The pathogenesis of human chronic rhinosinusitis with nasal polyps (CRSwNP) comprising eosinophilic CRSwNP (ECRSwNP) and non-eosinophilic (nECRSwNP) is not completely understood. Recent evidence has suggested that platelet-derived growth factor receptor alpha (PDGFRα) is implicated in cell growth, transformation, proliferation, migration, and vascular permeability and platelet-derived growth factor-A (PDGF-A) is a specific ligand for PDGFRα. However, little is known about their roles in CRSwNP. Therefore, we aimed to investigate the expression and role of PDGFRα and PDGF-A in CRSwNP.
PDGFRα protein expression was investigated by immunohistochemistry method and messenger RNA (mRNA) expression of PDGFRα and PDGF-A were assessed by real-time polymerase chain reaction (PCR) in CRSwNP patients and control subjects. Moreover, the effects of various stimulators with different concentrations and time on PDGFRα were evaluated on nasal explant culture.
Quantitative analysis of immunostaining for PDGFRα showed an obvious elevation in immunolabeling of PDGFRα in CRSwNP groups compared with controls. Furthermore, PDGFRα protein was significantly stronger expressed in ECRSwNP group than nECRSwNP group and atopic patients showed stronger expression of PDGFRα protein than nonatopic patients. The mRNA of PDGFRα and PDGF-A were overexpressed in CRSwNP, especially in ECRSwNP. PDGFRα mRNA expression was closely related to PDGF-A mRNA. In nasal explant culture and stimulation, PDGFRα mRNA was augmented by interleukin 4 (IL-4), IL-5, or IL-1β respectively, but suppressed by IL-27.
PDGFRα may play a pivotal role in the pathophysiology of ECRSwNP and nECRSwNP by combining with PDGF-A. IL-4, IL-5, or IL-1β may be critical for PDGFRα gene expression.
人类伴鼻息肉慢性鼻-鼻窦炎（CRSwNP）包括嗜酸性粒细胞性CRSwNP（ECRSwNP）和非嗜酸性粒细胞性（nECRSwNP）的发病机制尚未完全明确。最近有证据表明，血小板衍生生长因子受体α（PDGFRα）参与细胞生长、转化、增殖、迁移及血管通透性，且血小板衍生生长因子-A（PDGF-A）是PDGFRα的特异性配体。然而，它们在CRSwNP中的作用鲜为人知。因此，我们旨在研究PDGFRα和PDGF-A在CRSwNP中的表达及作用。
采用免疫组织化学方法研究CRSwNP患者和对照受试者中PDGFRα蛋白表达，通过实时聚合酶链反应（PCR）评估PDGFRα和PDGF-A的信使核糖核酸（mRNA）表达。此外，在鼻外植体培养中评估不同浓度和时间的各种刺激物对PDGFRα的影响。
与对照组相比，CRSwNP组中PDGFRα免疫染色的定量分析显示PDGFRα免疫标记明显升高。此外，PDGFRα蛋白在ECRSwNP组中的表达明显强于nECRSwNP组，特应性患者的PDGFRα蛋白表达强于非特应性患者。CRSwNP中，尤其是ECRSwNP中，PDGFRα和PDGF-A的mRNA过表达。PDGFRα mRNA表达与PDGF-A mRNA密切相关。在鼻外植体培养和刺激中，PDGFRα mRNA分别被白细胞介素4（IL-4）、IL-5或IL-1β增强，但被IL-27抑制。
PDGFRα可能通过与PDGF-A结合在ECRSwNP和nECRSwNP的病理生理过程中起关键作用。IL-4、IL-5或IL-1β可能对PDGFRα基因表达至关重要。
