摘要
目的:探讨胶原蛋白三螺旋重复序列1(CTHRC1)调控非经典Wnt信号通路在慢性阻塞性肺病(COPD)上皮–间质转化(EMT)进程中的作用。方法:使用GSE130928和GSE151052数据库确定CTHRC1在COPD病人和健康对照者肺组织样本中表达情况。通过香烟烟雾(CS)或香烟烟雾提取物(CSE)暴露模拟COPD小鼠模型和细胞模型,通过蛋白质印迹检测CTHRC1和EMT标志物表达。结果:GSE130928和GSE151052中,COPD病人肺组织中CTHRC1表达明显高于对照组(P<0.01)。CS组小鼠肺组织中CTHRC1蛋白表达高于对照组(P<0.05)。在暴露于CS 12周后,小鼠肺组织中E–钙黏蛋白表达下调(P<0.05),而波形蛋白表达上调(P<0.05)。CSE暴露导致HBE细胞中E–钙黏蛋白表达降低(P<0.01),波形蛋白表达增加(P<0.01)。CTHRC1敲低逆转了CSE刺激的HBE细胞中E–钙黏蛋白和波形蛋白改变(P<0.01),通过下调β–catenin途径缓解CSE诱导的EMT(P<0.01),由CTHRC1敲低引起的EMT诱导转录因子β–catenin、p–β–catenin变化可以被活化剂LiCl部分逆转(P<0.01)。结论:CTHRC1可以通过Wnt/β–catenin信号转导介导COPD进程中EMT的发展。
Objective:To investigate the role of collagen triple helix repeat containing 1(CTHRC1)in the process of epithelial-mesenchymal transition(EMT)in chronic obstructive pulmonary disease(COPD)by regulating the non-canonical Wnt signalingpathway.Methods:The expression levels of CTHRC1 in lung tissue samples from COPD patients and healthy controls wereinvestigated using the GSE130928 and GSE151052 databases.The expression levels of CTHRC1 and EMT markers were detectedby Western blotting in COPD mouse models and cellular models by exposure to cigarette smoke(CS)or cigarette smoke extract(CSE).Results:In GSE130928 and GSE151052,the expression level of CTHRC1 in lung tissue of COPD patients was significantlyhigher than that of control group(P<0.01).Compared with the control group,the protein level of CTHRC1 in the CS group wassignificantly up-regulated(P<0.05).After 12 weeks of exposure to incense CS,the expression of E-cadherin was down-regulated inmouse lung tissue(P<0.05),whereas the expression of vimentin was up-regulated(P<0.05).The CSE exposure resulted in thedecreasing of E-cadherin expression in HBE cells(P<0.01),while the expression of vimentin increased(P<0.01).The CTHRC1knockdown significantly reversed the changes in E-cadherin and vimentin in CSE-stimulated HBE cells,which could alleviate CSE-induced EMT by downregulating theβ-catenin pathway,and the changes in EMT-inducing transcriptional factorβ-catenin,p-β-catenin caused by CTHRC1 knockdown could be partly reversed by the activator lithium chloride.Conclusions:CTHRC1 canmediate the development of EMT in COPD progression through Wnt/β-catenin signaling.
作者
王欣
李海银
朱应群
李喆
范杜
WANG Xin;LI Haiyin;ZHU Yingqun;LI Zhe;FAN Du(Department of Respiratory and Critical Care Medicine,Changsha Third Hospital,Changsha Hunan 410000,China)
出处
《蚌埠医科大学学报》
2026年第2期141-146,共6页
Journal of Bengbu Medical University
基金
湖南省卫生健康委员会科研项目(20210243)。
关键词
慢性阻塞性肺疾病
胶原蛋白三螺旋重复序列1
上皮–间质转化
WNT信号通路
chronic obstructive pulmonary disease
collagen triple helix repeat containing 1
epithelial-mesenchymal transition
Wnt signaling pathway
