转化生长因子-β1对人近端肾小管上皮细胞结缔组织生长因子表达的影响  

Expression of CTGF induced by TGF-β1 in human proximal renal epithelial cells

作　　者：邢静萍[1] 王伟铭[1] 赵青[1] 陈楠[1] 

机构地区：[1]上海第二医科大学附属瑞金医院肾内科,上海200025

出　　处：《肾脏病与透析肾移植杂志》2004年第6期534-538,共5页Chinese Journal of Nephrology,Dialysis & Transplantation

基　　金：上海市科委重大项目基金 (NO :0 3JC14 0 84);上海市卫生局医学领先专业学科基金 (NO :983 0 0 9)资助项目

摘　　要：目的 :探讨转化生长因子 β1(TGF β1)对人肾小管上皮细胞结缔组织生长因子 (CTGF)表达的影响 ,同时观察TGF β1对肾小管上皮细胞合成细胞外基质 (ECM)、组织金属蛋白酶抑制剂 1(TIMP 1)及α 平滑肌肌动蛋白(α SMA)的影响。　 方法 :应用逆转录 聚合酶链反应 (RT PCR)技术 ,观察TGF β1诱导人近端肾小管上皮细胞系(HK 2 )合成CTGF、ECM、TIMP 1及α SMA的情况。　 结果 :在无TGF β1刺激的情况下 ,HK 2细胞中有基础量的CTGFmRNA表达 ,TGF β1以剂量和时间依赖的方式诱导HK 2细胞合成CTGFmRNA ,其表达在 2 4h时达高峰 ,同时TGF β1可使HK 2细胞合成ECM、α SMA增多 ,但在时相上均晚于CTGF。随着TGF β1浓度的增加 ,HK 2细胞合成TIMP 1也随之增加 ,但较大剂量的TGF β1(15ng/ml)方可使TIMP 1mRNA的表达明显增加 (P <0 0 5 )。　 结论 :TGF β1可直接诱导体外培养的人近端肾小管上皮细胞表达CTGF ,其表达转录水平要早于ECM、α SMA的表达 ,提示CTGF可能介导了TGF β1的促肾小管上皮细胞ECM合成和转分化的作用。Objective:To investigate the expression of connective tissue growth factor (CTGF) as well as extra-cellular matrix (ECM), tissue metalloproteinase-1 (TIMP-1), and α-smooth muscle actin (α-SMA) induced by TGF-β1 in cultured human proximal renal epithelial cells (HK-2 cells). Methodology:HK-2 cells were cultured with the concentrations of 0.05, 1, 5 10 and 15ng/ml TGF-β1 for 24 hours or treated with 5ng/ml TGF-β1 for 0, 6, 12, 24, 48, and 72 hours. The expression of CTGF, fibronectin, type Ⅰ collagen, TIMP-1 and α-SMA was measured by reverse transcription-polymerase chain reaction (RT-PCR). Results:The expression of CTGF was detected in the absence of TGF-β1 in HK-2 cells. TGF-β1 induced CTGF expression in a dose and time- dependent manner, which reached its highest level at the dose of 10ng/ml TGF-β1 and 24 hours after stimulation of 5ng/ml TGF-β1. TGF-β1 also induced the accumulation of ECM and expression of α-SMA, while the up-regulation of ECM and α-SMA stimulated by TGF-β1 was later than that of CTGF at the transcription level. Although the expression of TIMP-1 increased with the increasing of TGF-β1, its expression was not significant until TGF-β1 was 15 ng/ml(P<0.05). Conclusion:TGF-β1 induced CTGF expression in HK-2 cells in a dose and time- dependent manner, which was early than that of ECM andα-SMA. CTGF may mediate the deposition of ECM and the epithelial-myofibroblast trans-differentiation induced by TGF-β1.

关 键 词：转化生长因子-Β1 肾小管上皮细胞 结缔组织生长因子 表达 终末期肾病 

分 类 号：R692[医药卫生—泌尿科学]