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首页> 外文期刊>Acta Pharmacologica Sinica >Effect of transforming growth factor-beta on activity of connective tissue growth factor gene promoter in mouse NIH/3T3 fibroblasts
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Effect of transforming growth factor-beta on activity of connective tissue growth factor gene promoter in mouse NIH/3T3 fibroblasts

机译：转化生长因子β对小鼠NIH / 3T3成纤维细胞结缔组织生长因子基因启动子活性的影响

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AIM: To investigate the regulatory mechanism of transforming growth factor-beta on activity of connective tissue growth factor promoter in mouse NIH/3T3 fibroblasts. METHODS: The regulation fragment of the 5′ flanking region of the human CTGF gene was linked to pGL3-Basic vector, a firefly luciferase reporter construct without promoter. The recombinant plasmid pCTGF-luc was transiently transfected to NIH/3T3 fibroblasts. The activity of CTGF promoter after treatment of TGF-β_1 and MAPK pathway inhibitors were assayed with luciferase reporter gene assay system. RESULTS: TGF-β_1-induced increase of CTGF promoter activity was concentration-dependent, with a plateau at 5 μg/L by 2.67-fold vs control (P<0.05). The TGF-β_1, stimulation of CTGF promoter activity was time-dependent, too. After exposure to TGF-β_1, (5 μg/L), the maximal level of luciferase activity was reached at 12 h and maintained to 24 h by 2.76- and 2.20-fold vs control, respectively (P<0.05). Blockade of mitogen-activated protein kinases (MAPK) pathway with PD98059 (10 μmol/L), the MAP kinase kinase 1 inhibitor, and SB203580 (10 μmol/L), the p38 MAP kinase inhibitor, decreased basal and TGF-β_1-induced activation of CTGF promoter. However, inhibition of c-Jun-N-terminal kinase/stress-activated protein kinase by SP600125 (20 μmol/L) was without effect. CONCLUSION: TGF-β_1 stimulated the transcriptional activity of CTGF gene promoter in NIH/3T3 fibroblasts in a dose- and time-dependent manner. MAPK pathway may play a role in the regulation of TGF-β_1-induced CTGF expression.
机译：目的：探讨转化生长因子β对小鼠NIH / 3T3成纤维细胞结缔组织生长因子启动子活性的调控机制。方法：将人CTGF基因5'侧翼区的调控片段与pGL3-Basic载体连接，该载体是没有启动子的萤火虫荧光素酶报告基因构建体。将重组质粒pCTGF-luc瞬时转染至NIH / 3T3成纤维细胞。用荧光素酶报告基因检测系统检测TGF-β_1和MAPK途径抑制剂治疗后CTGF启动子的活性。结果：TGF-β_1诱导的CTGF启动子活性增加是浓度依赖性的，与对照相比，稳定在5μg/ L处为2.67倍（P <0.05）。 TGF-β_1，CTGF启动子活性的刺激也是时间依赖性的。暴露于TGF-β_1（5μg/ L）后，荧光素酶活性的最大水平在12 h达到，与对照相比分别保持2.76倍和2.20倍保持在24 h（P <0.05）。 MAP激酶激酶1抑制剂PD98059（10μmol/ L）和p38 MAP激酶抑制剂SB203580（10μmol/ L）阻断丝裂原激活的蛋白激酶（MAPK）途径，降低基础和TGF-β_1诱导激活CTGF启动子。但是，SP600125（20μmol/ L）抑制c-Jun-N-末端激酶/应力激活蛋白激酶无效。结论：TGF-β_1刺激NIH / 3T3成纤维细胞中CTGF基因启动子的转录活性呈剂量和时间依赖性。 MAPK途径可能在调节TGF-β_1诱导的CTGF表达中起作用。

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