晚期糖基化终产物受体对转化生长因子-β1引起肺泡上皮-间充质转化的影响  

Inhibitory effect of receptor for advanced glycation end products on the TGF-β_1-induced alveolar epithelial to mesenchymal transition

作　　者：丁辉[1] 陈如华[1] 唐志伟[1] 马铁梁[1] 陆勤[1] 冯艳[1] 

机构地区：[1]江苏大学附属宜兴医院呼吸内科,江苏宜兴214200

出　　处：《江苏大学学报（医学版）》2015年第5期399-403,共5页Journal of Jiangsu University：Medicine Edition

基　　金：江苏省卫生厅面上科研课题(YG201408)

摘　　要：目的:研究晚期糖基化终产物受体(receptor for advanced glycation end products,RAGE)对转化生长因子-β1(transforming growth factorβ1,TGF-β1)引起人肺腺癌A549细胞上皮-间充质转化(epithelial to mesenchymal transition,EMT)的影响。方法:体外培养人肺腺癌A549细胞,随机分为对照组、TGF-β1组、TGF-β1+AGE组、TGF-β1+AGE+sRAGE组,分别加入PBS、TGF-β1(5 ng/m L)、TGF-β1(5 ng/m L)+晚期糖基化终产物(advanced glycation end products,AGE,200μg/m L),TGF-β1(5 ng/m L)+AGE(200μg/m L)+可溶性RAGE(soluble RAGE,sRAGE,25μg/m L);蛋白质印迹检测各组细胞平滑肌肌动蛋白α(smooth muscle actin-α,α-SMA)、胶原-Ⅰ(Col-Ⅰ)蛋白表达及c-Jun氨基末端激酶(c-Jun N-terminal kinase,JNK)和细胞外信号调节激酶(extracellular signal-regulated kinases,ERK)磷酸化水平。结果:与对照组相比,TGF-β1组A549细胞RAGE蛋白表达明显降低(P<0.05),α-SMA、Col-Ⅰ蛋白表达明显增多(P<0.01),ERK1/2和JNK磷酸化水平明显提高(P<0.01);与TGF-β1组相比,TGF-β1+AGE组Col-Ⅰ,α-SMA蛋白表达明显减少(P<0.05),ERK1/2和JNK磷酸化水平明显降低(P<0.05);与TGF-β1+AGE组相比,TGF-β1+AGE+sRAGE组α-SMA、Col-Ⅰ蛋白表达明显增多(P<0.01),且ERK1/2和JNK磷酸化水平提高(P<0.01)。结论:RAGE可抑制TGF-β1诱导的A549肺腺癌细胞上皮-间充质转化。Objective:To investigate the inhibitory effect of receptor for advanced glycation end products (RAGE)on the transforming growth factor beta1 (TGF-β1 )-induced alveolar epithelial to mesenchymal transition (EMT)in A549 cells.Methods:A549 cells were divided into four groups:control group,TGF-β1 group,TGF-β1 +AGE group and TGF-β1 +AGE +sRAGE group,cells were treated with PBS,TGF-β1 (5 ng/mL),TGF-β1 (5 ng/mL)+advanced glycation end products(AGE,200 μg/mL),TGF-β1 (5 ng/mL)+AGE(200 μg/mL)+soluble RAGE (sRAGE,25 μg/mL).Proteins of smooth muscle actin-α(α-SMA),collagen-Ⅰ(Col-Ⅰ),phosphorylated c-Jun N-terminal kinase (JNK)and extracellular signal-reg-ulated kinases (ERK)induced by TGF-β1 were detected by Western blotting.Results:Compared with the control group,RAGE protein level was significantly decreased in A549 cells in TGF-β1 group (P <0.05), meanwhile expressions of α-SMA and Col-I were inereased obviously (P <0.01 ).Moreover,increased phosphorylation of ERK1 /2 and JNK were found in A549 cells in TGF-β1 group (P <0.01).An addition of AGE reduced TGF-β1-stimulated α-SMA and Col-I expression (P <0.05 )in TGF-β1 +AGE group,&nbsp;compared with the TGF-β1 group;meanwhile,AGE markedly attenuated phosphorylation of ERK1 /2 and JNK (P <0.05).Moreover,TGF-β1 +AGE +sRAGE group showed higher expression levels of α-SMA and Col-Ⅰ,phosphorylated ERK 1 /2 and JNK than TGF-β1 +AGE group (P <0.01 ).Conclusion:RAGE inhibited TGF-β1-induced EMT in A549 cells.

关 键 词：转化生长因子-Β1 晚期糖基化终产物受体 Α-平滑肌肌动蛋白 上皮-间充质转化 

分 类 号：R563[医药卫生—呼吸系统]