MG132抑制TGF-β1诱导的人肺成纤维细胞活化  

MG132 inhibits TGF-β1-induced activation of human lung fibroblasts

作　　者：曹述任 杨俊侠[1] 张敏[1] 

机构地区：[1]暨南大学第四附属医院广州市红十字会医院呼吸内科,广东广州510220

出　　处：《基础医学与临床》2016年第2期156-160,共5页Basic and Clinical Medicine

基　　金：国家自然科学基金(81100042);广东省医学科研基金(A2012498)

摘　　要：目的探讨泛素-蛋白酶体抑制剂MG132对转化生长因子β1(TGF-β1)诱导人肺成纤维细胞活化的影响及机制。方法体外培养人胚肺成纤维细胞(MRC-5),随机分为对照组、TGF-β1组(10μg/L)和MG132(0.5μmol/L)处理组。Western blot法检测细胞α-平滑肌肌动蛋白(α-SMA)和Ⅰ型胶原α1(COL1A1)的表达;RT-PCR和Western blot法分别检测细胞Smad7、核转录共抑制因子SnoN、TGF-βI型受体(TβRI)、Smad2和Smad3 mRNA及蛋白的表达。结果与对照组比较,TGF-β1促进了α-SMA和COL1A1蛋白表达(P<0.05),MG132抑制了TGF-β1的上述作用(P<0.05)。TGF-β1组Smad7和SnoN mRNA表达较对照组增加(P<0.05)。TGF-β1组Smad7和SnoN蛋白表达较对照组减少(P<0.05),而MG132组Smad7和SnoN蛋白水平较TGF-β1组增加(P<0.05)。结论 MG132可能通过阻止Smad7和SnoN蛋白泛素化降解,抑制TGF-β1诱导人肺成纤维细胞活化。Objective To investigate the effect of ubiquitin-proteasome inhibitor MG132 on TGF-β1-induced activation in lung fibroblasts and its mechanism. Methods Human embryonic lung fibroblasts（ MRC-5） were randomly divided into three groups as follows： control group,TGF-β1 group and MG132 group. The protein level ofα-SMA and COL1A1 was detected by Western blot. The mRNA and protein expression of Smad7,SnoN（ Ski-related novel gene N）,TβRI,Smad2 and Smad3 were detected by RT-PCR and Western blot respectively. Results TGF-β1 treatment of lung fibroblasts increased α-SMA and COL1 A1 expression（ P 〈 0. 05）. MG132 inhibited TGF-β1-induced α-SMA and COL1 A1 expression in lung fibroblasts（ P 〈 0. 05）. The mRNA level of Smad7 and SnoN in TGF-β1 group increased（ P 〈 0. 05）. The protein level of Smad7 and SnoN in TGF-β1 group decreased（ P 〈 0. 05）. Compared with TGF-β1 group,the protein level of Smad7 and SnoN in MG132 group increased（ P 〈 0. 05）. Conclusions MG132 inhibits TGF-β1-induced activation in lung fibroblasts in vitro,which may be associated with the inhibitory effect of MG132 on TGF-β / Smads signaling by preventing degradation of Smad7 and SnoN.

关 键 词：泛素-蛋白酶体抑制剂 成纤维细胞 转化生长因子β1 SMAD7 SNON 

分 类 号：R563[医药卫生—呼吸系统]