Potential Involvement of the Epidermal Growth Factor Receptor Ligand Epiregulin and Matrix Metalloproteinase-1 in Pathogenesis of Chronic Rhinosinusitis.
Potential Involvement of the Epidermal Growth Factor Receptor Ligand Epiregulin and Matrix Metalloproteinase-1 in Pathogenesis of Chronic Rhinosinusitis.
复制标题
表皮生长因子受体配体上皮调节蛋白和基质金属蛋白酶-1 在慢性鼻窦炎发病机制中的潜在参与。
DOI：
10.1165/rcmb.2016-0325oc
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发表时间：
2017
影响因子：
6.4
通讯作者：
Conl
中科院分区：
文献类型：
--
作者：
Homma,Tetsuya;Kato,Atsushi;Sakashita,Masafumi;Takabayashi,Tetsuji;Norton,JamesE;Suh,LydiaA;Carter,RoderickG;Harris,KathleenE;Peters,AnjuT;Grammer,LeslieC;Min,Jin-Young;Shintani-Smith,Stephanie;Tan,BruceK;Welch,Kevin;Conl
慢性鼻窦炎 (CRS) 是一种发生在鼻子和鼻旁窦的异质性慢性炎症性疾病，可伴有或伴有鼻息肉 (CRSwNP)。 CRSwNP 的显着特征是频繁出现 2 型过敏性炎症和金黄色葡萄球菌 (SA) 定植率高。尽管采取了积极的医疗治疗，但随着炎症持续存在，鼻窦组织仍会经历上皮损伤和修复以及息肉生长。由于受损组织的特征之一是生长因子信号传导增强，因此我们评估了 CRS 中表皮生长因子受体 (EGFR) 配体和基质金属蛋白酶 (MMP) 的存在。本研究的目的是分析 CRS 患者中 EGFR 配体和 MMP 的表达，并探讨 SA 对上皮活化的可能作用。在手术期间从对照受试者和患有慢性鼻窦炎的患者身上收集鼻腔组织。如前所述对组织进行处理，以分析组织提取物中大多数 EGFR 配体的 mRNA (RT-PCR) 和蛋白质 (ELISA)。 CRS 组织用于通过免疫组织化学评估表皮调节蛋白 (EREG)（一种 EGFR 配体）和 MMP-1 的分布。在平行研究中，分析了培养的原代气道上皮细胞中这些基因和蛋白质的表达。在 CRSwNP 患者的钩突和息肉组织中观察到 EREG 和 MMP-1 mRNA 和蛋白的表达升高。临床样本的免疫组织化学研究表明，气道上皮细胞表达这两种蛋白质。培养的原代人气道上皮细胞表达MMP-1，并且通过EREG或热灭活SA（HKSA）刺激进一步诱导MMP-1。 HKSA 对 MMP-1 的诱导被针对 EREG 的抗体阻断，表明内源 EREG 在 HKSA 刺激后诱导 MMP-1。研究发现 CRSwNP 患者的鼻息肉和钩状组织中的 EREG 和 MMP-1 升高。 EREG 和 MMP-1 表达升高可能与 CRS 中息肉的形成有关，而 SA 的定植可能会进一步增强这一过程。
Chronic rhinosinusitis (CRS) is a heterogeneous chronic inflammatory disease of the nose and paranasal sinuses that presents without or with nasal polyps (CRSwNP). Notable features of CRSwNP are the frequent presence of type 2 allergic inflammation and high prevalence ofStaphylococcus aureus(SA) colonization. As inflammation persists, sinus tissue undergoes epithelial damage and repair along with polyp growth, despite active medical management. Because one feature of damaged tissue is enhancement of growth factor signaling, we evaluated the presence of epidermal growth factor receptor (EGFR) ligands and matrix metalloproteinases (MMPs) in CRS. The objectives of this study were to analyze the expression of EGFR ligands and MMPs in patients with CRS and to investigate the possible role of SA on epithelial activation. Sinonasal tissues were collected during surgery from control subjects and patients with CRS. Tissues were processed as described previously for analysis of mRNA (RT-PCR) and proteins (ELISA) for the majority of EGFR ligands within the tissue extracts. CRS tissue was used for evaluation of the distribution of epiregulin (EREG), an EGFR ligand, and MMP-1 by immunohistochemistry. In parallel studies, expression of these genes and proteins was analyzed in cultured primary airway epithelial cells. Elevated expression of EREG and MMP-1 mRNA and protein was observed in uncinate and polyp tissue from patients with CRSwNP. Immunohistochemistry study of clinical samples revealed that airway epithelial cells expressed both of these proteins. Cultured primary human airway epithelial cells expressed MMP-1, and MMP-1 was further induced by stimulation with EREG or heat-killed SA (HKSA). The induction of MMP-1 by HKSA was blocked by an antibody against EREG, suggesting that endogenous EREG induces MMP-1 after stimulation with HKSA. EREG and MMP-1 were found to be elevated in nasal polyp and uncinate tissues in patients with CRSwNP. Elevated expression of EREG and MMP-1 may be related to polyp formation in CRS, and colonization of SA might further enhance this process.