UNASSIGNED: To elucidate the role of eosinophils in inducing fibrin deposition in CRS nasal polyp tissues and explore potential regulatory mechanisms.
UNASSIGNED: We analyzed the expression of genes related to the serpin family and fibrinolytic system using Gene Expression Omnibus and Next-generation sequencing data. Differentially expression genes (DEGs) analysis was used to compare control and nasal polyp tissues, followed by KEGG and Gene ontology (GO) analysis. We measured the expression and correlation of plasminogen activator-1 (PAI-1), tissue plasminogen activator (t-PA), urokinase plasminogen activator (u-PA), and urokinase plasminogen activator surface receptor (u-PAR) in CRS tissues, and evaluated the effect of eosinophils on the fibrinolytic system using a cytokine array and co-culture.
UNASSIGNED: Nasal polyp tissues showed upregulated PAI-1, u-PA, and u-PAR expression and downregulated t-PA expression. Fibrinolytic system-related genes positively correlated with Th2 cytokines, except for t-PA. Eosinophil-derived Chitinase-3-like protein 1 (CHI3L1) increased PAI-1 expression and decreased t-PA levels in fibroblasts and epithelial cells. The inhibition of CHI3L1 suppresses these alterations.
UNASSIGNED: CHI3L1 contributes to fibrin deposition by impairing the fibrinolytic system during nasal polyp formation. The regulation of CHI3L1 expression may inhibit fibrin deposition and edema in ECRS, presenting a potential treatment for this condition.
■阐明嗜酸性粒细胞在诱导CRS鼻息肉组织纤维蛋白沉积中的作用,并探索潜在的调节机制。
■我们使用基因表达Omnibus和下一代测序数据分析了与serpin家族和纤溶系统相关的基因的表达。差异表达基因(DEGs)分析用于比较对照和鼻息肉组织,其次是KEGG和基因本体论(GO)分析。我们测量了纤溶酶原激活物-1(PAI-1)的表达和相关性,组织纤溶酶原激活剂(t-PA),尿激酶型纤溶酶原激活剂(u-PA),和CRS组织中的尿激酶纤溶酶原激活物表面受体(u-PAR),并使用细胞因子阵列和共培养评估嗜酸性粒细胞对纤溶系统的影响。
■鼻息肉组织显示PAI-1,u-PA上调,和u-PAR表达和下调的t-PA表达。纤溶系统相关基因与Th2细胞因子呈正相关,除了T-PA。嗜酸性粒细胞衍生的几丁质酶-3样蛋白1(CHI3L1)增加了成纤维细胞和上皮细胞中PAI-1的表达并降低了t-PA的水平。CHI3L1的抑制抑制了这些改变。
■CHI3L1通过在鼻息肉形成过程中损害纤溶系统而有助于纤维蛋白沉积。调节CHI3L1的表达可能抑制ECRS中的纤维蛋白沉积和水肿,为这种情况提供了潜在的治疗方法。