骨膜蛋白:哮喘患者气道上皮功能异常的原因?
2020/09/18
摘要
骨膜蛋白（Periostin）可以作为哮喘中2型介导的嗜酸性粒细胞气道炎症的生物标志物。我们推测，2型细胞因子IL-13诱导了呼吸道上皮中骨膜蛋白的表达，而骨膜蛋白又参与了哮喘中观察到的上皮细胞的改变。我们研究了IL-13对BEAS-2B和气液界面(ALI)分化的原代支气管上皮细胞(PBECs)中骨膜蛋白表达的影响。此外，还评估了重组人骨膜蛋白对上皮-间充质转化(EMT)标记物和粘蛋白基因的影响。在哮喘患者和健康对照组支气管活检和诱导痰标本中，我们分析了骨膜蛋白单细胞基因表达以及蛋白水平。IL-13增加了两种细胞的POSTN表达，在BEAS-2B中伴有上皮-间充质转化相关特征。在气液界面分化的PBECs中，IL-13增加了基底外侧和根尖周围骨膜蛋白的释放。在支气管活检中，根尖给予骨膜蛋白可增加MMP9、MUC5B和MUC5AC的表达，POSTN表达主要局限于基底上皮细胞、离子细胞、内皮细胞和成纤维细胞，显示哮喘患者的基底上皮细胞表达高于对照组。与健康对照组相比，哮喘患者的支气管活检证实，上皮和上皮下层中表达的骨膜蛋白水平较高。尽管哮喘患者的痰中骨膜蛋白水平不高，但其水平与嗜酸性粒细胞数量和咳出粘液相关。IL-13在支气管上皮细胞中增加了骨膜蛋白的表达，在哮喘患者的支气管活组织检查中也升高了。这可能会产生重要的结果，由于给予骨膜蛋白会增加上皮粘蛋白基因的表达，支持了骨膜蛋白与2型介导的哮喘和粘液分泌之间的关系。
Periostin: contributor to abnormal airway epithelial function in asthma?
Janette K Burgess, Marnix R Jonker, Marijn Berg, Nick T H Ten Hacken, Kerstin B Meyer，Maarten van den Berge, Martijn C Nawijn, Irene H Heijink
Abstract
Periostin may serve as a biomarker for type-2-mediated eosinophilic airway inflammation in asthma. We hypothesised that type-2 cytokine IL-13 induces airway epithelial expression of periostin, which in turn contributes to epithelial changes observed in asthma.We studied the effect of IL-13 on periostin expression in BEAS-2B and air-liquid interface (ALI)-differentiated primary bronchial epithelial cells (PBECs). Additionally, effects of recombinant human periostin on epithelial-to-mesenchymal transition (EMT) markers and mucin genes were assessed. In bronchial biopsies and induced sputum from asthma patients and healthy controls, we analysed periostin single cell gene expression and protein levels.IL-13 increased POSTN expression in both cell types, which was accompanied by EMT-related features in BEAS-2B. In ALI-differentiated PBECs, IL-13 increased periostin basolateral and apical release. Apical administration of periostin increased the expression of MMP9, MUC5B and MUC5AC In bronchial biopsies, POSTN expression was mainly confined to basal epithelial cells, ionocytes, endothelial cells and fibroblasts, showing higher expression in basal epithelial cells from asthma patients versus controls. Higher protein levels of periostin, expressed in epithelial and subepithelial layers, was confirmed in bronchial biopsies from asthma patients compared to healthy controls. Although sputum periostin levels were not higher in asthma, levels correlated with eosinophil numbers and coughing up mucus. Periostin expression is increased by IL-13 in bronchial epithelial cells and higher in bronchial biopsies from asthma patients. This may have important consequences, as administration of periostin increased epithelial expression of mucin genes, supporting the relationship of periostin with type-2 mediated asthma and mucus secretion.
骨膜蛋白（Periostin）可以作为哮喘中2型介导的嗜酸性粒细胞气道炎症的生物标志物。我们推测，2型细胞因子IL-13诱导了呼吸道上皮中骨膜蛋白的表达，而骨膜蛋白又参与了哮喘中观察到的上皮细胞的改变。我们研究了IL-13对BEAS-2B和气液界面(ALI)分化的原代支气管上皮细胞(PBECs)中骨膜蛋白表达的影响。此外，还评估了重组人骨膜蛋白对上皮-间充质转化(EMT)标记物和粘蛋白基因的影响。在哮喘患者和健康对照组支气管活检和诱导痰标本中，我们分析了骨膜蛋白单细胞基因表达以及蛋白水平。IL-13增加了两种细胞的POSTN表达，在BEAS-2B中伴有上皮-间充质转化相关特征。在气液界面分化的PBECs中，IL-13增加了基底外侧和根尖周围骨膜蛋白的释放。在支气管活检中，根尖给予骨膜蛋白可增加MMP9、MUC5B和MUC5AC的表达，POSTN表达主要局限于基底上皮细胞、离子细胞、内皮细胞和成纤维细胞，显示哮喘患者的基底上皮细胞表达高于对照组。与健康对照组相比，哮喘患者的支气管活检证实，上皮和上皮下层中表达的骨膜蛋白水平较高。尽管哮喘患者的痰中骨膜蛋白水平不高，但其水平与嗜酸性粒细胞数量和咳出粘液相关。IL-13在支气管上皮细胞中增加了骨膜蛋白的表达，在哮喘患者的支气管活组织检查中也升高了。这可能会产生重要的结果，由于给予骨膜蛋白会增加上皮粘蛋白基因的表达，支持了骨膜蛋白与2型介导的哮喘和粘液分泌之间的关系。
(中日友好医院呼吸与危重症医学科 张清 摘译 林江涛 审校)
(Eur Respir J. 2020 Sep 9;2001286. doi: 10.1183/13993003.01286-2020.)
(Eur Respir J. 2020 Sep 9;2001286. doi: 10.1183/13993003.01286-2020.)
Periostin: contributor to abnormal airway epithelial function in asthma?
Janette K Burgess, Marnix R Jonker, Marijn Berg, Nick T H Ten Hacken, Kerstin B Meyer，Maarten van den Berge, Martijn C Nawijn, Irene H Heijink
Abstract
Periostin may serve as a biomarker for type-2-mediated eosinophilic airway inflammation in asthma. We hypothesised that type-2 cytokine IL-13 induces airway epithelial expression of periostin, which in turn contributes to epithelial changes observed in asthma.We studied the effect of IL-13 on periostin expression in BEAS-2B and air-liquid interface (ALI)-differentiated primary bronchial epithelial cells (PBECs). Additionally, effects of recombinant human periostin on epithelial-to-mesenchymal transition (EMT) markers and mucin genes were assessed. In bronchial biopsies and induced sputum from asthma patients and healthy controls, we analysed periostin single cell gene expression and protein levels.IL-13 increased POSTN expression in both cell types, which was accompanied by EMT-related features in BEAS-2B. In ALI-differentiated PBECs, IL-13 increased periostin basolateral and apical release. Apical administration of periostin increased the expression of MMP9, MUC5B and MUC5AC In bronchial biopsies, POSTN expression was mainly confined to basal epithelial cells, ionocytes, endothelial cells and fibroblasts, showing higher expression in basal epithelial cells from asthma patients versus controls. Higher protein levels of periostin, expressed in epithelial and subepithelial layers, was confirmed in bronchial biopsies from asthma patients compared to healthy controls. Although sputum periostin levels were not higher in asthma, levels correlated with eosinophil numbers and coughing up mucus. Periostin expression is increased by IL-13 in bronchial epithelial cells and higher in bronchial biopsies from asthma patients. This may have important consequences, as administration of periostin increased epithelial expression of mucin genes, supporting the relationship of periostin with type-2 mediated asthma and mucus secretion.
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哮喘中嗜酸性粒细胞捕获病毒的能力受损
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