HIGH EXPRESSION OF THE PRO-RENIN RECEPTOR IN ALDOSTERONE PRODUCING ADENOMA CAUSING HUMAN PRIMARY ALDOSTERONISM: 4D.02
HIGH EXPRESSION OF THE PRO-RENIN RECEPTOR IN ALDOSTERONE PRODUCING ADENOMA CAUSING HUMAN PRIMARY ALDOSTERONISM: 4D.02
复制标题
肾素原受体在产生醛固酮的腺瘤中高表达导致人类原发性醛固酮增多症：4D.02
DOI：
10.1097/01.hjh.0000378861.66448.71
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发表时间：
2010
影响因子：
4.9
通讯作者：
G. P. Rossi
中科院分区：
文献类型：
--
作者：
C. Recarti;T. Seccia;L. Lenzini;G. Skander;B. Caroccia;Pessina Ac;G. P. Rossi
目的：原发性醛固酮增多症（PA）是内分泌性高血压最常见的形式，但其潜在机制尚不清楚。尽管肾素受到抑制，但在PA患者血浆中检测到prorenin，提示prorenin通过前肾素受体（prorenin Receptor， PRR）作用，可能通过引起肾上腺皮质细胞生长和高醛固酮增多症，在PA中发挥病理生理作用。因此，我们假设PRR在人肾小球带（ZG）和醛固酮产生腺瘤（APA）中表达。设计和方法：为了验证这一假设，我们事先使用全转录组分析方法调查了PRR的存在（在24 APA）。然后，我们使用Real time RT-PCR更精确地定量了APA （n = 12）、两种肾上腺皮质癌细胞系（H295和HAC15）和免疫磁珠分离CD56+人肾上腺皮质ZG细胞中的PRR转录本（Caroccia, Endocrinology 2010）。为了证实PRR在蛋白水平上的表达，还进行了免疫组织化学和免疫印迹分析。结果与结论：基因芯片分析证实了PRR在所有APAs中的表达。定量基因表达研究表明，PRR基因在APA中的表达水平平均远高于已建立的肾上腺皮质管家基因PBGD （PRR Ct = 22,69±1,11;PBGD Ct = 27,49±1,69 p < 0.0001）。PRR在人肾上腺皮质组织中的表达在CD56+ ZG细胞、H295和HAC15细胞中得到证实。免疫组化证实了PRR在蛋白水平上的表达。它还可以更精确地定位到肾上腺皮质ZG。这些结果与循环prorenin可以激活PA患者PRR的假设是一致的。因此，实验正在进行中，以研究这些发现的功能相关性，最终目标是证明PRR在人类PA中的作用。
Objective: Primary Aldosteronism (PA) is the most prevalent form of endocrine hypertension but its underlying mechanisms are unknown. The detection of prorenin, despite the suppression of renin, in plasma of PA patients suggests that prorenin, by acting via the Pro-Renin Receptor (PRR), could play a pathophysiologic role in PA by causing adrenocortical cell growth and hyperaldosteronism. Hence, we hypothesized that the PRR is expressed in the human zona glomerulosa (ZG) and in aldosterone producing adenoma (APA). Design and Method: To test this hypothesis we investigated the presence of the PRR by using beforehand a whole transcriptome analysis approach (in 24 APA). We then used Real time RT-PCR to quantify more precisely the PRR transcript in APA (n = 12), in two adrenocortical carcinoma cell lines (H295 and HAC15) and in immunomagnetic bead separated CD56+ human adrenocortical ZG cells (Caroccia, Endocrinology 2010). To confirm the expression of the PRR at the protein level immunohistochemistry and immunoblotting were also performed. Results and Conclusions: Microarray analysis evidenced the expression of PRR in all APAs. Quantitative gene expression studies demonstrated a level of expression of the PRR gene in APA which was on average much higher than that of the established adrenocortical house-keeping gene PBGD (PRR Ct = 22,69 ± 1,11; PBGD Ct = 27,49 ± 1,69 p < 0.0001). The expression of the PRR in the human adrenal cortical tissue was confirmed in CD56+ ZG cells, and in H295 and HAC15 cells. Immunohistochemistry confirmed the expression of the PRR at the protein level in all these cells. It also allowed to localize it more precisely to the adrenocortical ZG. These results are consistent with the hypothesis that circulating prorenin can activate the PRR in PA patients. Therefore, experiments are ongoing to investigate the functional relevance of these findings with the ultimate goal of demonstrating the role of the PRR in human PA.