TGF-β1对甲状腺相关性眼病眼眶成纤维细胞外基质基因表达的影响  

Effect of transforming growth factor-β1 on gene expression of extracellular matrix components in orbital fibroblasts with thyroid-associated ophthalmopathy

作　　者：陆燕[1] 张鹏[2] 魏锐利[1] 蔡季平[1] 吴颖[1] 

机构地区：[1]第二军医大学附属长征医院眼科 , 上海市200003 [2]第二军医大学神经生物教研室张鹏,上海市 200433

出　　处：《眼科新进展》2011年第4期308-311,共4页Recent Advances in Ophthalmology

基　　金：国家自然科学基金面上项目(编号:81070758)~~

摘　　要：目的探讨转化生长因子-β1(transforming growth factor-β1,TGF-β1)对甲状腺相关性眼病(thyroid-associated ophthalmopathy,TAO)患者眼外肌来源成纤维细胞(orbital fi-broblasts,OF)细胞外基质(extracellular matrix,ECM)主要成分金属蛋白酶组织抑制剂-1(tissue inhibitors of metalloproteinases-1,TIMP-1)、胶原Ⅰ(collagen typeⅠ,COL-Ⅰ)、胶原Ⅲ(collagen typeⅢ,COL-Ⅲ)及纤维连接蛋白(fibronectin,FN)基因表达水平的影响。方法采用实时荧光定量逆转录聚合酶链反应(RT-PCR)观察10μg·L-1TGF-β1刺激OF后不同时间点(0h、3h、6h、12h、24h、48h)及不同浓度TGF-β1(1μg·L-1、5μg·L-1、10μg·L-1、20μg·L-1)刺激OF24h后TIMP-1、COL-I、COL-Ⅲ及FN mRNA表达的变化。结果 10μg·L-1TGF-β1刺激OF的时间效应:TIMP-1mRNA在3h和6h分别为对照组的1.50倍和2.46倍(P<0.01);COL-ⅠmRNA在24h和48h分别为对照组的5.49、3.69倍(P<0.01);COL-ⅢmRNA在24h和48h分别为对照组的2.14、1.63倍(P<0.01);FN mRNA在12h和24h后分别为对照组的2.45、1.53倍(P<0.01)。不同浓度TGF-β1刺激OF24h后剂量效应:与空白对照组相比,TIMP-1mRNA在5μg·L-1和10μg·L-1时分别为空白对照组的1.79、1.46倍(P<0.01);COL-ⅠmRNA在1μg·L-1和10μg·L-1分别空白对照组的1.94、3.29倍(P<0.01);COL-ⅢmRNA在5μg·L-1和10μg·L-1分别空白对照组的1.52、3.28倍(P<0.01);FN mRNA在1μg·L-1和10μg·L-1分别为空白对照组的1.30、2.45倍(P<0.01)。结论 TGF-β1以剂量和时间依赖的方式刺激OF表达TIMP-1、COL-Ⅰ、COL-Ⅲ及FN mRNA,TGF-β1可能在TAO眼外肌纤维化机制中发挥了重要的作用。Objective To investigate the effects of transforming growth factor-β1（TGF-β1） on gene expression of main components of extracellular matrix including tissue inhibitions of metalloproteinase-1（TIMP-1）,collagen type-I（COL-I）,COL-Ⅲ and fibronectin（FN） in orbital fibroblasts（OF） of patients with thyroid-associated ophthalmopathy（TAO）. Methods OF were treated with 10 μg·L-1 TGF-β1 at different time points（0 hour,3 hours,6 hours,12 hours,24 hours and 48 hours） and different concentrations（1 μg·L-1,5 μg· L-1 ,10 μg · L-1 and 20 μg ·L-1 ） of TGF-β1 for 24 hours,and real-time quantitative RT-PCR was performed to observe the effects of TGF-βI on the expression of TIMP-1, COL- I , COL-Ⅲ and FN mRNA.Rlesults Time effect of OF treated with 10 pug · L-1 TGF-βI ：TIMP-1 mRNA was 1.5 folds to that of control group at 3 hours and 2.45 folds at 6 hours（ both P 〈 0.01 ） ; COL-I mRNA was 5.49 folds to that of control group at 24 hours and 3.59 folds at 48 hours（both P 〈0.01 ） ;COL-]][ mRNA was 2.14 folds to that of control group at 24 hours and 1.53 folds at 48 hours（ both P 〈 0.01 ） ;FN mRNA was 2.45 folds to that of control group at 12 hours and 1.53 folds at 24 hours（both P 〈0.01 ） ;Dose effects of OF treated with different concentrations TGF- βl for 24 hours：TIMP-1 mRNA was 1.79 folds to that of control group at 5 μg · L-1 and 1.45 folds at l0 pug · L- 1 （ both P 〈 0.01 ） ; COL-I mRNA was 1.94 folds to that of control group at 1 μg · L-1 and 3.29 folds at l0μg . L-1 （both P 〈0.01 ） ;COL-IU mRNA was 1.52 folds to that of control group at 5 }~g ~ L-1 and 3.28 folds at l0 μg · L-1 （ both P 〈 0. 01 ） ;FN mRNA was 1.30 folds to that of control group at 1 pug ~ L-1 and 2.45 folds at 10 μg ·L-1 （ both P 〈 0.01 ）. Conclusions TGF-β1 can stimulate the expression of TIMP-1 ,COL- I ,COL-Ⅲ and FN in OF in a time and dose-dependent manner. It may play an important role in the pathogenesis of extraocular muscle fibrosis with

关 键 词：转化生长因子-Β1 成纤维细胞 甲状腺相关性眼病 细胞外基质 

分 类 号：R771.3[医药卫生—眼科]