Pinet Florence, Poirier Florence, Fuchs Sébastien, Tharaux Pierre-Louis, Caron Michel, Corvol Pierre, Michel Jean-Baptiste, Joubert-Caron Raymonde
INSERM U508, Pasteur Institute, 1 rue du professeur Calmette, 59019 Lille cedex, France.
FASEB J. 2004 Mar;18(3):585-6. doi: 10.1096/fj.03-0939fje. Epub 2004 Jan 8.
Renovascular hypertension is characterized by stenosis of the renal artery and high plasma renin levels. The renal phenotype is characterized by high levels of renin in the hypoperfused kidney due to the recruitment of renin-producing cells along the afferent arterioles. This increase in myoepithelioïd cells is due mainly to the differentiation of existing smooth muscle cells with acquisition of a secretory phenotype. To understand the molecular mechanisms involved in this recruitment, we used the established rat model of renovascular hypertension known as the two-kidney, one-clip model in the Lewis rat. Renal arterioles were isolated using magnetized iron suspension. Differential proteomic analysis was performed using 2-D polyacrylamide gel electrophoresis followed by mass spectrometry. Comparative analysis of soluble proteins extracted from afferent arterioles of clipped and contralateral kidneys showed 14 proteins significantly differentially expressed by at least a factor of 2. These proteins were identified by mass spectrometry. The most striking protein revealed by proteomics is troponin T, which is down-regulated in the afferent arterioles of the clipped kidney. Confocal microscopy showed that troponin T is specific of the smooth muscle phenotype and absent in the myoepithelioïd phenotype. Our data suggest that troponin T is only present in renal smooth muscle cells.
肾血管性高血压的特征是肾动脉狭窄和血浆肾素水平升高。肾脏表型的特征是由于沿入球小动脉的肾素产生细胞募集,导致灌注不足的肾脏中肾素水平升高。肌上皮样细胞的这种增加主要是由于现有平滑肌细胞的分化并获得了分泌表型。为了了解参与这种募集的分子机制,我们使用了已建立的肾血管性高血压大鼠模型,即Lewis大鼠中的两肾一夹模型。使用磁化铁悬浮液分离肾小动脉。使用二维聚丙烯酰胺凝胶电泳随后进行质谱分析进行差异蛋白质组学分析。对从夹闭侧肾脏和对侧肾脏的入球小动脉中提取的可溶性蛋白质进行比较分析,结果显示有14种蛋白质的表达差异至少为2倍。这些蛋白质通过质谱鉴定。蛋白质组学揭示的最显著的蛋白质是肌钙蛋白T,它在夹闭侧肾脏的入球小动脉中下调。共聚焦显微镜显示肌钙蛋白T是平滑肌表型所特有的,在肌上皮样表型中不存在。我们的数据表明肌钙蛋白T仅存在于肾平滑肌细胞中。