Expression and Functional Analysis of CST1 in Intractable Nasal Polyps
Expression and Functional Analysis of CST1 in Intractable Nasal Polyps
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DOI：
10.1165/rcmb.2017-0325oc
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发表时间：
2018-10-01
影响因子：
6.4
通讯作者：
Fujieda, Shigeharu
中科院分区：
文献类型：
--
作者：
Kato, Yukinori;Takabayashi, Tetsuji;Fujieda, Shigeharu
在这项研究中，我们发现Cystatin SN（CST1），一种2型半胱氨酸蛋白酶抑制剂亚家族成员，在顽固性慢性鼻窦炎（CRS）伴鼻息肉患者的鼻息肉中高度表达，使用下一代测序的全转录本分析。嗜酸性粒细胞性CRS（ECRS）涉及鼻息肉，鼻息肉是难治性的，在内窥镜鼻窦手术后立即复发。我们推测，CST 1可能有助于ECRS的发病机制。我们通过实时PCR和免疫组织化学方法检测了ECRS患者鼻息肉中CST1的表达。与未患ECRS的鼻息肉患者（非ECRS）相比，ECRS患者鼻息肉上皮细胞中CST 1的表达显著增加。特别是，CST1在重度ECRS患者中表现出非常强的表达。CST1的表达可能与ECRS的复发性和难治性有关。我们使用鼻上皮细胞和鼻成纤维细胞检测了CST1的功能。IL-4+双链RNA + CST1的组合刺激显著升高鼻上皮细胞中TSLP的mRNA表达水平和蛋白水平。TSLP或IL-33刺激显著提高鼻上皮细胞中CST1的mRNA表达水平。CST1的刺激显著提高了鼻成纤维细胞中CCL11和POST1的mRNA表达水平。CST1可通过与鼻息肉上皮细胞源性细胞因子和成纤维细胞相互作用，放大嗜酸性粒细胞浸润和辅助性T细胞2型炎症。CST1可能参与了ECRS的发病机制，并可能与鼻息肉术后CRS的严重程度和复发有关。
In this study, we found Cystatin SN (CST1), a type 2 cystatin subfamily member, to be highly expressed in nasal polyps from patients with intractable chronic rhinosinusitis (CRS) with nasal polyps, using a whole-transcript analysis with next-generation sequencing. Eosinophilic CRS (ECRS) involves nasal polyps that are refractory and recur immediately after endoscopic sinus surgery. We hypothesized that CST1 may contribute to the pathogenesis of ECRS. We examined the expression of CST1 in nasal polyps from patients with ECRS by assessing mRNA expression levels using real-time PCR and immunohistochemistry. CST1 showed significantly greater expression in the epithelial cells of nasal polyps from patients with ECRS than in those from patients who did not have ECRS (non-ECRS). In particular, CST1 showed very strong expression in patients with severe ECRS. The expression of CST1 may be correlated with the recurrent and refractory nature of ECRS. We examined the function of CST1 using nasal epithelial cells and nasal fibroblasts. Stimulation by a combination of IL-4 plus double-stranded RNA plus CST1 significantly elevated mRNA expression levels and protein levels of TSLP in nasal epithelial cells. Stimulation by TSLP or IL-33 significantly elevated mRNA expression levels of CST1 in nasal epithelial cells. Stimulation of CST1 significantly elevated mRNA expression levels of CCL11 and POSTN in nasal fibroblasts. CST1 could amplify eosinophilic infiltration and T-helper cell type 2 inflammation by interacting with epithelial-derived cytokines and fibroblasts on nasal polyps. CST1 may be involved in the pathogenesis of ECRS, and may contribute to the severity and recurrence of CRS with nasal polyps after endoscopic sinus surgery.