Adrenal (Pro)renin Receptor Expression and Serum Soluble (Pro)renin Receptor Concentration in Primary Aldosteronism

Abstract

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 β-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.

Soluble (Pro)Renin Receptor Level in Patients with Severe Obesity Is Associated with Visceral Adiposity and Is Involved with Insulin Resistance and Renal Injury

“…Regarding the relationship between blood s(P)RR levels and metabolic and renal function factors, Hamada et al [ 18 ] reported higher blood s(P)RR levels in CKD patients with type 2 diabetes and hypertension. Watanabe et al [ 34 ] reported that blood s(P)RR levels are associated with renal damage in patients with primary aldosteronism, and Morimoto et al [ 16 ] reported that blood s(P)RR levels are associated with the severity of renal damage in patients with essential hypertension. These reports and the results of the present study may suggest that the s(P)RR is involved in insulin resistance and renal glomerular damage associated with obesity.…”

Advanced Oxidation Protein Product Promotes Oxidative Accentuation in Renal Epithelial Cells via the Soluble (Pro)renin Receptor‐Mediated Intrarenal Renin‐Angiotensin System and Nox4‐H2O2 Signaling

“…fPRR belongs to the type I transmembrane receptor family, characterized by containing an interesting 28 kDa soluble PRR (sPRR) and generated by site-1 protease (S1P) [ 16 , 17 ]. Intensive clinical studies have proven that sPRR levels are significantly upregulated in various diseases and disease models, such as severe heart failure, hemodialysis maintenance, and primary aldosteronism, thus suggesting the value of sPRR as a biomarker [ 18 – 21 ]. sPRR is hypothesized to bind to specific ligands and receptors and mediate many signal transduction pathways [ 22 – 30 ].…”

Mapping the protein binding site of the (pro)renin receptor using in silico 3D structural analysis

“…(P)RR protein levels are elevated in the subfornical organ of the brain of hypertensive humans [ 56 ], and brain (P)RR can regulate blood pressure by altering prohypertensive and antihypertensive pathways through local angiotensin-II-dependent and angiotensin-II-independent mechanisms [ 2 ]. Adrenal gland (P)RR is anticipated to contribute to adrenal aldosterone synthesis and the pathogenesis of hypertension [ 2 , 57 ], although the precise mechanism leading to the enhancement of aldosterone production remains unknown. In this study, we proposed that the IDR-containing hydrophobic grooves act as a protein binding site of (P)RR and allow multiple protein interactions.…”