Yu Shengyou
a Guangzhou Medical University, Guangzhou First People's Hospital , Guangdong Province , China.
J Recept Signal Transduct Res. 2016;36(1):1-5. doi: 10.3109/10799893.2014.963872. Epub 2014 Sep 29.
To investigate the function of nephrin in podocytes and its relation to proteinuria in kidney diseases, and to study more clearly theoretical basis for the molecular mechanism of losartan anti-proteinuria and the special beneficial effects of losartan on podocyte injury.
Experiment set up control, Ang II and losartan group. Cell morphology was observed perturbation, and using image processing software to analyze the cell body of cell morphology and size of the difference after 8 h, 24 h and 48 h. Detecting nephrin mRNA and protein expression changes by real time PCR (RT-PCR) and western blotting at different time points.
Podocyte cell bodies were significantly reduced after Ang II injury (p < 0.01), losartan directly reduces the rate of apoptotic podocytes induced by Ang. Apoptotic podocytes may related to the decrease of nephrin mRNA and protein expressions, losartan reduced the apoptosis and proteinuria by declining nephrin mRNA and protein expressions.
Ang II induced podocyte injury caused abnormal expression and distribution of nephrin in podocytes, losartan maybe maintain the stability of nephrin expression and the integrity of hole diaphragm (SD) structure and function by blocking the signal path, playing a important role in protection mechanisms of anti-proteinuria. Our findings provide some possible clues for further exploring the pharmacological targets to the proteinuria. These novel findings provide new insights into the beneficial effects of losartan on podocytes directly.
探讨nephrin在足细胞中的功能及其与肾脏疾病蛋白尿的关系,更清楚地研究氯沙坦抗蛋白尿分子机制及氯沙坦对足细胞损伤特殊有益作用的理论基础。
实验设对照组、Ang II组和氯沙坦组。观察细胞形态扰动,利用图像处理软件分析8小时、24小时和48小时后细胞形态和细胞体大小的差异。通过实时PCR(RT-PCR)和蛋白质印迹法在不同时间点检测nephrin mRNA和蛋白质表达变化。
Ang II损伤后足细胞细胞体显著减少(p < 0.01),氯沙坦直接降低Ang诱导的足细胞凋亡率。凋亡的足细胞可能与nephrin mRNA和蛋白质表达降低有关,氯沙坦通过降低nephrin mRNA和蛋白质表达减少凋亡和蛋白尿。
Ang II诱导的足细胞损伤导致足细胞中nephrin表达和分布异常,氯沙坦可能通过阻断信号通路维持nephrin表达的稳定性及裂孔隔膜(SD)结构和功能的完整性,在抗蛋白尿保护机制中起重要作用。我们的研究结果为进一步探索蛋白尿的药理学靶点提供了一些可能的线索。这些新发现为氯沙坦对足细胞的直接有益作用提供了新的见解。