川北医学院学报2017，Vol.32Issue(5)：649-655,7.DOI:10.3969/j.issn.1005-3697.2017.05.001
粒状头样2在肺纤维化上皮间质转化中的作用研究
Research of GRHL2 in epithelial mesenchymal transition of pulmonary fibrosis
摘要
Abstract
Objective:To explore the function of grainyheas-like2 (GRHL2) on the epithelial-mesenchymal transition (EMT) in pulmonary fibrosis rats.Methods:45 rats were randomly divided into normal control group,model group and sodium valproate group,15 rats in each group.Rats in the model group and sodium valproate group were injected with bleomycin along air tube to construct pulmonary fibrosis model,and rats in the normal control group was given the same amount of normal saline by the same method.The rats were injected with 200 mg ·kg-1·d-1 sodium valproate by intraperitoneally in sodium valproate group,the rats were injected with the same amount of normal saline in the normal control group and the model group for 28 d continuously.The pathological changes of lung tissue was detected by HE staining.The fibrosis of lung tissue was detected by Masson staining.The content of hydroxyproline (HYP) was detected by alkaline hydrolysis.The expression of GRHL2 was detected by immunohistochemistry and Western blot.The expression of EMT related protein E-cadherin,alpha smooth muscle cell actin (α-SMA),Vimentin,Wnt/β-catenin signaling pathway related proteins was detected by Western blot.Results:Compared with the normal control group,the alveolar structure of lung tissue was destroyed,a large number of collagen fibers were deposited,the collagen staining area ratio,Ashcroft score and HYP content were increased (P ＜ 0.01),the positive rate and expression of GRHL2 was decreased (P ＜ 0.01),the expression of E-cadherin was down-regulated (P ＜ 0.01),the expression of α-SMA,Vimentin,β-catenin,lymphoid enhancer-binding (LEF1) and matrix metalloproteinase 7 (MMP7) up-regulated in model group (P ＜ 0.01).Compared with the model group,the structure of alveolar tissue was more complete,the degree of collagen fiber deposition was lighter,the collagen staining area ratio,Ashcroft score and HYP content decreased (P ＜ 0.01),the positive rate and expression of GRHL2 was increased (P ＜ 0.01),the expression of E-cadherin was up-regulated (P ＜0.01),the expression of α-SMA,Vimentin,β-catenin,LEF1 and MMP7 down-regulated (P ＜ 0.01).Conclusion:In rats with pulmonary fibrosis,the expression of GRHL2 is down regulated,which activates the Wnt/beta-catenin signaling pathway,promotes the formation of EMT and aggravates the pulmonary fibrosis in rats,and valproate can reverse the process.关键词
粒状头样2(GRHL2)/丙戊酸钠/肺纤维化/大鼠/上皮间质转化(EMT)/Wnt/β-catenin信号通路Key words
Grainyheas-like2 (GRHL2)/Sodium valproate/Pulmonary fibrosis/Rats/Epithelial-mesenchymal transition (EMT)/Wnt/β-catenin signaling pathway分类
医药卫生引用本文复制引用
孙建,代文静,邱静,李万成..粒状头样2在肺纤维化上皮间质转化中的作用研究[J].川北医学院学报,2017,32(5):649-655,7.基金项目
四川省教育厅科研计划项目(16ZB0292) （16ZB0292）
