TGFBR1基因调控Wnt/β-catenin信号通路对结缔组织病相关的肺间质病变中抗纤维化的机制研究  

Anti fibrosis mechanism of TGFBR1 gene by regulating Wnt/β-catenin signaling pathway in connective tissue disease interstitial lung disease

作　　者：岳彩芳[1] 付冰冰[1] 骆鹏[1] YUE Cai-Fang;FU Bing-Bing;LUO Peng(First Affiliated Hospital of Jiamusi University,Jiamusi 154002,China)

机构地区：[1]佳木斯大学附属第一医院,佳木斯154002

出　　处：《中国免疫学杂志》2018年第9期1394-1399,共6页Chinese Journal of Immunology

摘　　要：目的:探讨TGF-β受体Ⅰ(TGFBR1)基因调控Wnt/β-catenin信号通路对结缔组织病相关的肺间质病变(CTD-ILD)的抗纤维化作用。方法:以肺癌的癌旁组织作为正常对照组,Western blot检测CTD-ILD患者肺组织TGFBR1的蛋白表达;人胚肺成纤维细胞系MRC-5分为空白对照组、TGF-β1组、阴性对照组和TGFBR1-siRNA组,各组细胞培养48 h,Western blot检测TGFBR1、Ⅰ型胶原、结缔组织生长因子(CTGF)、α-平滑肌肌动蛋白(α-SMA)、E-钙黏蛋白(E-Cad)及Wnt/β-catenin信号通路β-连环蛋白(β-catenin)和c-Myc的蛋白表达;CCK8法检测各组细胞的活力。结果:TGFBR1在CTD-ILD肺组织中的表达显著高于正常肺组织(P<0. 05);与空白对照组比较,TGF-β1组细胞活力、TGFBR1、Ⅰ型胶原、CTGF、α-SMA、β-catenin和c-Myc的蛋白表达均显著升高,E-cad蛋白表达显著降低(P<0. 05);TGF-β1组和阴性对照组细胞活力、TGFBR1、Ⅰ型胶原、CTGF、α-SMA、E-cad、β-catenin和c-Myc的蛋白表达差异均无统计学意义(P> 0. 05);与TGF-β1组比较,TGFBR1-siRNA组细胞活力、TGFBR1、Ⅰ型胶原、CTGF、α-SMA、β-catenin和c-Myc的蛋白表达均显著降低,E-cad蛋白表达显著升高(P<0. 05)。结论:TGFBR1基因在CTD-ILD肺组织中表达升高,抑制TGFBR1的表达可通过下调Wnt/β-catenin信号通路降低CTD-ILD纤维化的发生。Objective:To investigate the anti fibrosis effect of TGFBR1 gene by regulating Wnt/β-catenin signaling pathway on connective tissue disease interstitial lung disease(CTD-ILD).Methods:The adjacent tissues of lung cancer were used as normal control group,TGFBR1 protein expression in lung tissue of CTD-ILD patients was detected by Western blot;human embryonic lung fibroblast cell line MRC-5 were divided into control group,TGF-β1 group,negative control group and TGFBR1-siRNA group,cells were cultured for 48 h,the expression of TGFBR1,collagen typeⅠ,CTGF,α-SMA,E-cad and Wnt/β-catenin signaling pathwayβ-catenin and c-Myc were detected by Western blot;cell viability was detected by CCK8 assay.Results:The expression of TGFBR1 in lung tissue of CTD-ILD was significantly higher than that in normal lung tissue(P<0.05);compared with the control group,cell viability and the expression of TGFBR1,typeⅠcollagen,CTGF,α-SMA,β-catenin and c-Myc protein in TGF-β1 group were significantly increased,E-cad protein expression decreased significantly(P<0.05);there was no significant difference in cell viability and the expression of TGFBR1,typeⅠcollagen,CTGF,α-SMA,E-cad,β-catenin and c-Myc between TGF-β1 group and negative control group(P>0.05);Compared with the TGF-β1 group,cell viability and the expression of TGFBR1,typeⅠcollagen,CTGF,α-SMA,β-catenin and c-Myc protein in TGFBR1-siRNA group were significantly increased,the expression of E-cad protein increased significantly(P<0.05).Conclusion:The expression of TGFBR1 gene is increased in CTD-ILD lung tissues,and the inhibition of TGFBR1 expression may reduce the occurrence of CTD-ILD fibrosis by down regulating the Wnt/β-catenin signaling pathway.

关 键 词：TGFBR1基因 结缔组织病相关的肺间质病变 纤维化 信号通路 

分 类 号：R563.9[医药卫生—呼吸系统]