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外基质基因骨膜蛋白在慢性鼻-鼻窦炎中的表达增加,并在内镜鼻窦手术后降低。

Expression of the extracellular matrix gene periostin is increased in chronic rhinosinusitis and decreases following successful endoscopic sinus surgery.

机构信息

Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), CHUM-Hotel Dieu Hospital, Montreal, QC, Canada.

出版信息

Int Forum Allergy Rhinol. 2012 Nov;2(6):471-6. doi: 10.1002/alr.21056. Epub 2012 Jun 13.

Abstract

BACKGROUND

The extracellular matrix (ECM) is a potentially important component of mucosal immunity. ECM dysregulation in chronic rhinosinusitis (CRS) is suggested by genomewide association studies identifying ECM genes as top candidates. Further support is afforded by the demonstration of increased expression of periostin (POSTN) in CRS biopsy samples compared to controls, and by reported roles in eosinophilic inflammation and steroid responsiveness. We wished to evaluate the potential utility of POSTN as a biomarker for disease activity by determining whether POSTN levels were modified in disease and whether they were modulated by endoscopic sinus surgery (ESS).

METHODS

Twelve patients undergoing ESS for CRS and 10 controls undergoing ESS for skull-base access were recruited. An epithelial sample from the frontal recess was collected using a cytology brush at time of and 3 months after surgery. Microarray analysis of gene expression was performed using the Illumina HumanHT-12 Beadchip v3. POSTN protein level in biopsy samples taken from the same place of brushings at surgery was analyzed by immunohistochemistry (IHC) staining.

RESULTS

All patients resolved CRS with ESS. At surgery, a higher expression of POSTN was seen in the CRS group compared to controls (fold change [FC] = 4.89, positive false discovery rate (pFDR) = 0.0006), which was also verified by IHC. After ESS, POSTN expression in CRS group decreased (FC = -3.074, pFDR = 0.0044), and was no longer different from controls (FC = 1.56, pFDR = 0.3).

CONCLUSION

Demonstration of reduced levels in the expression of POSTN, an ECM gene, following resolution of disease, implicates POSTN, a potential pathogenesis indicator or biomarker of CRS disease activity and responsiveness to treatment.

摘要

背景

细胞外基质(ECM)是黏膜免疫的一个潜在重要组成部分。全基因组关联研究鉴定 ECM 基因是候选基因,提示慢性鼻-鼻窦炎(CRS)中 ECM 失调。在 CRS 活检样本中与对照相比,骨膜蛋白(POSTN)表达增加,以及在嗜酸性粒细胞炎症和类固醇反应性中报道的作用,进一步支持了这一观点。我们希望通过确定 POSTN 水平是否在疾病中发生改变以及是否受内镜鼻窦手术(ESS)调节,来评估 POSTN 作为疾病活动生物标志物的潜在效用。

方法

招募了 12 例因 CRS 而行 ESS 的患者和 10 例因颅底入路而行 ESS 的对照。在手术时和手术后 3 个月,使用细胞学刷从额隐窝采集上皮样本。使用 Illumina HumanHT-12 Beadchip v3 进行基因表达的微阵列分析。在手术时从相同刷取部位采集的活检样本中通过免疫组织化学(IHC)染色分析 POSTN 蛋白水平。

结果

所有患者均通过 ESS 治愈 CRS。在手术时,CRS 组 POSTN 的表达高于对照组(倍数变化 [FC] = 4.89,阳性错误发现率(pFDR)= 0.0006),这也通过 IHC 得到了验证。在 ESS 之后,CRS 组 POSTN 的表达减少(FC = -3.074,pFDR = 0.0044),并且与对照组无差异(FC = 1.56,pFDR = 0.3)。

结论

在疾病缓解后,细胞外基质基因 POSTN 的表达水平降低,提示 POSTN 是 CRS 疾病活动和对治疗反应的潜在发病机制指标或生物标志物。

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