Watanabe Daisuke, Morimoto Satoshi, Morishima Noriko, Kato Yoichiro, Nagashima Yoji, Shibata Noriyuki, Ichihara Atsuhiro
Department of Endocrinology and Hypertension, Tokyo Women's Medical University, 8-1 Kawada-Cho, Shinjuku-Ku, Tokyo 162-8666, Japan.
Department of Pathology, Tokyo Women's Medical University, 8-1 Kawada-Cho, Shinjuku-Ku, Tokyo 162-8666, Japan.
Int J Endocrinol. 2020 Sep 28;2020:9640103. doi: 10.1155/2020/9640103. eCollection 2020.
The (pro)renin receptor [(P)RR] is a multifunctioning protein playing roles in various pathological conditions. A soluble form of (P)RR [s(P)RR] has been considered a biomarker for (P)RR expression in tissues. Expression of (P)RR has been described in aldosterone-producing adenoma (APA), but the roles of (P)RR have yet to be fully determined. This study investigated the significance of (P)RR and serum s(P)RR concentrations in patients with APA. We evaluated associations between (P)RR expression and expression of CYP11B2, an aldosterone synthase, and aldosterone production by the adrenal glands and assessed the relationships between serum s(P)RR concentration and background factors. (P)RR colocalized with CYP11B2 and expression levels of (P)RR were positively associated with those of CYP11B2 in APA tissues. (P)RR immunoreactivity in these tissues correlated positively with plasma aldosterone concentrations (PAC) and urinary aldosterone excretion. Also, in APA, (P)RR mRNA abundance was positively correlated with -catenin mRNA abundance. Significant positive correlations were identified between serum s(P)RR concentration and plasma glucose, hemoglobin A1c, and serum creatinine levels, but not with PAC (in either peripheral vein or adrenal vein) or adrenal (P)RR expression level. This study showed that (P)RR expression level correlates with CYP11B2 expression in APA tissues and PAC and urinary aldosterone excretion, suggesting that (P)RR expression may contribute to aldosterone synthesis via CYP11B2 activation in APAs, although serum s(P)RR concentration failed to show any significant relationship with adrenal (P)RR expression. Adrenal (P)RR activity might offer a therapeutic target in the treatment of PA, although this issue needs to be investigated in future studies.
（前）肾素受体[（P）RR]是一种多功能蛋白，在多种病理状态中发挥作用。（P）RR的可溶性形式[s（P）RR]被认为是组织中（P）RR表达的生物标志物。醛固酮分泌性腺瘤（APA）中已有（P）RR表达的描述，但（P）RR的作用尚未完全明确。本研究调查了APA患者中（P）RR及血清s（P）RR浓度的意义。我们评估了（P）RR表达与醛固酮合酶CYP11B2的表达以及肾上腺醛固酮产生之间的关联，并评估了血清s（P）RR浓度与背景因素之间的关系。在APA组织中，（P）RR与CYP11B2共定位，且（P）RR的表达水平与CYP11B2的表达水平呈正相关。这些组织中的（P）RR免疫反应性与血浆醛固酮浓度（PAC）及尿醛固酮排泄呈正相关。此外，在APA中，（P）RR mRNA丰度与β-连环蛋白mRNA丰度呈正相关。血清s（P）RR浓度与血浆葡萄糖、糖化血红蛋白及血清肌酐水平之间存在显著正相关，但与（外周静脉或肾上腺静脉中的）PAC或肾上腺（P）RR表达水平无关。本研究表明，APA组织中（P）RR表达水平与CYP11B2表达以及PAC和尿醛固酮排泄相关，提示（P）RR表达可能通过激活APA中的CYP11B2促进醛固酮合成，尽管血清s（P）RR浓度与肾上腺（P）RR表达未显示出任何显著关系。肾上腺（P）RR活性可能为原发性醛固酮增多症的治疗提供一个治疗靶点，尽管这一问题有待未来研究进一步探讨。
