转化生长因子β1通过赖氨酰氧化酶调控低氧诱导的大鼠支气管上皮细胞间充质转化

doi:10.3969/j.issn.1000-4718.2019.12.021

科研成果详情

题名	转化生长因子β1通过赖氨酰氧化酶调控低氧诱导的大鼠支气管上皮细胞间充质转化
其他题名	Transforming growth factor-β_1 regulates hypoxia-induced bronchial epithelial- mesenchymal transition by activation of lysys oxidase
作者	夏晓东; 彭燕平; 雷丹; 陈伟谦
发表日期	2019-12-15
发表期刊	中国病理生理杂志影响因子和分区
语种	中文
原始文献类型	学术期刊
关键词	低氧支气管上皮细胞转化生长因子β_1 赖氨酰氧化酶上皮-间充质转化
摘要	目的:探讨转化生长因子β_1(transforming growth factor-β_1,TGF-β_1)是否通过赖氨酰氧化酶(lysyl oxidase,LOX)参与低氧诱导的大鼠支气管上皮细胞间充质转化。方法:24只SD大鼠随机均分为常氧组、低氧组以及低氧+β-氨基丙腈(β-aminopropionitrile,β-APN)组。体外培养大鼠支气管上皮细胞,分为常氧组、TGF-β_1组、TGF-β_1+SB431542(TGF-β_1受体拮抗剂)组、低氧组、低氧+SB431542组以及低氧+β-APN组。比色法测定并计算胶原蛋白交联,免疫组织化学法和Western blot检测大鼠支气管上皮细胞TGF-β_1、LOX、E-钙黏蛋白(E-cadherin)以及波形蛋白(vimentin)的蛋白表达。结果:在大鼠动物模型中,低氧组支气管上皮细胞TGF-β_1、LOX、vimentin蛋白表达以及胶原交联均明显高于常氧组,但E-cadherin蛋白表达则明显弱于常氧组,低氧对vimentin、E-cadherin蛋白表达以及胶原交联的影响均能被β-APN所逆转。离体细胞实验显示,常氧组大鼠支气管上皮细胞为铺路石状形态,TGF-β_1组和低氧组大鼠支气管上皮细胞形态逐渐向梭形上皮间充质细胞转化,而β-APN能逆转大鼠支气管上皮间充质细胞转化。TGF-β_1能诱导大鼠支气管上皮细胞LOX蛋白表达,呈浓度依赖性,并被SB431542所阻断。与常氧组比较,低氧组离体培养的大鼠支气管上皮细胞TGF-β_1、LOX和vimentin表达及胶原交联明显升高,SB431542能明显下调TGF-β_1或低氧诱导的大鼠支气管上皮细胞LOX和vimentin的表达及胶原交联;TGF-β_1组和低氧组离体培养的大鼠支气管上皮细胞E-cadherin表达减弱,SB431542能逆转TGF-β_1或低氧培养的大鼠支气管上皮细胞E-cadherin的表达。结论:TGF-β_1介导LOX表达,促进低氧诱导的大鼠支气管上皮细胞间充质转化。
其他摘要	AIM:To investigate whether transforming growth factor-β_1(TGF-β_1) participates in hypoxia-induced bronchial epithelial-mesenchymal transition (EMT) through lysyl oxidase (LOX).METHODS:Sprague-Dawley(SD) rats were exposed to hypoxia to establish the animal model and were treated with LOX inhibitor β-aminopropionitrile(β-APN).Furthermore,primary rat bronchial epithelial cells were cultured in vitro and exposed either to normoxia or to hypoxia.TGF-β_1,TGF-β_1 receptor inhibitor (SB431542) or β-APN was used in the cell experiments.The content of collagen was measured by colorimetric method.The expression of TGF-β_1,LOX,and 2 EMT-related proteins (namely,the epithelial marker E-cadherin and the mesenchymal marker vimentin) were determined by immunohistochemistry and Western blot,respectively.RESULTS:The expression of TGF-β_1,vimentin and LOX and cross-linking of collagen were enhanced in hypoxia-exposed rat and in hypoxia-exposed bronchial epithelial cells,but the enhancement was impaired by the treatment with β-APN.In contrast,the expression of E-cadherin was reduced in hypoxia-exposed rat,and was reversed by treatment with β-APN.In vitro experiments demonstrated that TGF-β_1 and hypoxia led to the morphological phenotype characteristic of EMT in rat bronchial epithelial cells,in which the morphology of rat bronchial epithelial cells was switched from cobble-stone shape in normoxia-exposed group to spindle fibroblast-like morphology in hypoxia- or TGF-β_1-exposed group (P <0.01).Additionally,both β-APN and SB431542 partially prevented TGF-β_1 and hypoxia induced EMT in rat bronchial epithelial cells.TGF-β_1was able to dose-dependently up-regulate LOX expression in rat bronchial epithelial cells,which was blocked by concurrent incubation with SB431542.The up-regulation of TGF-β_1,vimentin,LOX and cross-linking of collagen and down-regulation of E-cadherin in hypoxia-exposed rat bronchial epithelial cells was significantly reversed by incubation with SB431542.CONCLUSION:TGF-β_1 regulates hypoxia-induced EMT in bronchial epithelial cells via activation of the LOX.
资助项目	浙江省自然科学基金资助项目（No.LY12H01002）;温州市科技计划资助项目（No.2017Y0182）
ISSN	1000-4718
卷号	35 期号:12 页码:2247-2254
DOI	10.3969/j.issn.1000-4718.2019.12.021
页数	8
收录类别	CNKI ; 万方 ; SCOPUS ; 维普 ; 北大核心 ; PKU ; CSCD ; ISTIC
学科领域	医药、卫生 ; 基础医学 ; 内科学
URL	查看原文
CSCD记录号	CSCD:6632338
SCOPUSEID	2-s2.0-85171421274
引用统计
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/43575
专题	第二临床医学院，附属第二医院、育英儿童医院_内科学_呼吸内科
作者单位	温州医科大学附属第二医院&育英儿童医院呼吸内科
第一作者单位	第二临床医学院，附属第二医院、育英儿童医院_内科学_呼吸内科
第一作者的第一单位	第二临床医学院，附属第二医院、育英儿童医院_内科学_呼吸内科
推荐引用方式 GB/T 7714	夏晓东,彭燕平,雷丹,等. 转化生长因子β1通过赖氨酰氧化酶调控低氧诱导的大鼠支气管上皮细胞间充质转化[J]. 中国病理生理杂志,2019,35(12):2247-2254.
APA	夏晓东, 彭燕平, 雷丹, & 陈伟谦. (2019). 转化生长因子β1通过赖氨酰氧化酶调控低氧诱导的大鼠支气管上皮细胞间充质转化. 中国病理生理杂志, 35(12), 2247-2254.
MLA	夏晓东,et al."转化生长因子β1通过赖氨酰氧化酶调控低氧诱导的大鼠支气管上皮细胞间充质转化".中国病理生理杂志 35.12(2019):2247-2254.