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转化生长因子β1对佩罗尼氏病成纤维细胞中单核细胞趋化蛋白-1 mRNA表达的上调作用

Upregulation of mRNA expression of MCP-1 by TGF-beta1 in fibroblast cells from Peyronie's disease.

作者信息

Szardening-Kirchner Carolin, Konrad Lutz, Hauck Ekkehard W, Haag Simone M, Eickelberg Oliver, Weidner Wolfgang

机构信息

Department of Urology, Medical Faculty, University Hospital Giessen, Justus Liebig University, Rudolf-Buchheim-Str. 7, 35392, Giessen, Germany.

出版信息

World J Urol. 2009 Feb;27(1):123-30. doi: 10.1007/s00345-008-0320-x. Epub 2008 Aug 14.

Abstract

INTRODUCTION

Peyronie's disease (PD) is a localized connective tissue disorder of the penile tunica albuginea (TA) with a still obscure etiopathology. Recent studies from our laboratory have demonstrated differences in Smad3 and Smad4 gene expression of PD-fibroblasts and non-PD-fibroblasts after stimulation with recombinant TGF-beta1 for 1 h. In the present study, we investigated gene expression of Smad2-Smad4 and Smad7 up to 6 h after stimulation with TGF-beta1. As a positive control, MCP-1 gene expression was monitored.

MATERIALS AND METHODS

Cells with fibroblast characteristics were isolated from seven PD plaques and three TA controls. The cells were incubated with recombinant TGF-beta1 for 2-6 h and expression of Smad2-Smad4, Smad7, and monocyte chemotactic protein-1 (MCP-1) was determined by quantitative real-time PCR.

RESULTS

TGF-beta1 treatment resulted in a statistically significant up-regulation of Smad7 and MCP-1 gene expression. Smad7 expression was increased after 2 h (P < 0.001) and was still high after 4 h (P < 0.05). No significant differences between fibroblasts from PD-patients compared to non-PD-patients were observed. MCP-1 peaked after 4 h (P < 0.001) and remained high up to 6 h (P < 0.01). PD-fibroblasts revealed a significantly increased MCP-1 gene expression compared to non-PD-fibroblasts (P = 0.013) after 2 h and remained significantly different also after 6 h (P = 0.038). Gene expression of Smad2-Smad4 did not change during stimulation with TGF-beta1.

CONCLUSION

In conclusion, analysis of MCP-1 expression might be a useful marker for Peyronie's disease.

摘要

引言

佩罗尼氏病(PD)是阴茎白膜(TA)的一种局部结缔组织疾病,其病因病理仍不清楚。我们实验室最近的研究表明,用重组转化生长因子-β1(TGF-β1)刺激1小时后,PD成纤维细胞和非PD成纤维细胞的Smad3和Smad4基因表达存在差异。在本研究中,我们研究了用TGF-β1刺激后长达6小时的Smad2 - Smad4和Smad7基因表达情况。作为阳性对照,监测了单核细胞趋化蛋白-1(MCP-1)基因表达。

材料与方法

从7个PD斑块和3个TA对照中分离出具有成纤维细胞特征的细胞。将细胞与重组TGF-β1孵育2 - 6小时,通过定量实时聚合酶链反应(PCR)测定Smad2 - Smad4、Smad7和单核细胞趋化蛋白-1(MCP-1)的表达。

结果

TGF-β1处理导致Smad7和MCP-1基因表达在统计学上显著上调。Smad7表达在2小时后增加(P < 0.001),4小时后仍很高(P < 0.05)。未观察到PD患者的成纤维细胞与非PD患者的成纤维细胞之间存在显著差异。MCP-1在4小时后达到峰值(P < 0.001),并在长达6小时内保持高水平(P < 0.01)。与非PD成纤维细胞相比,PD成纤维细胞在2小时后显示出MCP-1基因表达显著增加(P = 0.013),6小时后也仍有显著差异(P = 0.038)。在用TGF-β1刺激期间,Smad2 - Smad4的基因表达没有变化。

结论

总之,MCP-1表达分析可能是佩罗尼氏病的一个有用标志物。

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