Zhou Jing, Xu Fei, Yu Jing Jing, Zhang Wei
Department of Respiratory Medicine, The First Affiliated Hospital of Nanchang University 17 Yongwai, Donghu District, Nanchang 330006, Jiangxi, P.R. China.
Int J Clin Exp Pathol. 2015 Sep 1;8(9):11132-9. eCollection 2015.
Asthma is characterized by leukocytic infiltration and tissue remodeling with structural changes including subepithelial fibrosis and ASM cells proliferation. The Hippo pathway is a key regulatory point involved in cell proliferation, fibroblasts, and smooth muscle cell differentiation. In order to disclose the relation between asthma and the Hippo pathway, expression of the Yes-associated protein (YAP), a key gene in the Hippo pathway, in the bronchial smooth muscle of chronic asthma model (CAM) was studied. 40 mice were randomly divided into control (wide type) and experimental group to construct CAM using chicken ovalbumin (OVA). Pathological changes of the lung tissues were observed in the CAM mice compared with the control using HE staining method. Immunohistochemistry (IHC) was used to detect if YAP protein is expressed in the lung tissues. The pathological changes of the CAM group showed that a large number of inflammatory cells infiltration including mainly lymphocytes and a small amount of eosinophilic, with the presence of certain airway smooth muscle hyperplasia, was observed in comparison with the control. IHC results showed that the YAP protein was significantly increased compared with the control groups (P < 0.01). This result was further confirmed by quantitative real-time PCR (qPCR) assay which detected the up-regulation of the YAP gene (P < 0.01) and Western blot. In conclusion, the YAP protein was significantly expressed in the bronchial airway tissues of the CAM mice, and could be used as an indicator for asthma.
哮喘的特征是白细胞浸润和组织重塑，并伴有包括上皮下纤维化和气道平滑肌细胞增殖在内的结构变化。Hippo信号通路是参与细胞增殖、成纤维细胞和平滑肌细胞分化的关键调控点。为了揭示哮喘与Hippo信号通路之间的关系，研究了慢性哮喘模型（CAM）支气管平滑肌中Hippo信号通路关键基因Yes相关蛋白（YAP）的表达。将40只小鼠随机分为对照组（野生型）和实验组，用鸡卵清蛋白（OVA）构建CAM。采用苏木精-伊红（HE）染色法观察CAM小鼠肺组织的病理变化，并与对照组进行比较。采用免疫组织化学（IHC）检测肺组织中是否表达YAP蛋白。CAM组的病理变化显示，与对照组相比，观察到大量炎性细胞浸润，主要为淋巴细胞和少量嗜酸性粒细胞，伴有一定程度的气道平滑肌增生。IHC结果显示，与对照组相比，YAP蛋白显著增加（P<0.01）。定量实时聚合酶链反应（qPCR）检测到YAP基因上调（P<0.01），蛋白质免疫印迹法进一步证实了这一结果。总之，YAP蛋白在CAM小鼠的支气管气道组织中显著表达，可作为哮喘的一个指标。
