Collecting Duct Pro(Renin) Receptor Contributes to Unilateral Ureteral Obstruction-Induced Kidney Injury via Activation of the Intrarenal RAS.

Background: Although the concept of the intrarenal renin-angiotensin system (RAS) in renal disease is well-described in the literature, the precise pathogenic role and mechanism of this local system have not been directly assessed in the absence of confounding influence from the systemic RAS. The present study used novel mouse models of collecting duct (CD)-specific deletion of (pro)renin receptor (PRR) or renin together with pharmacological inhibition of soluble PRR production to unravel the precise contribution of the intrarenal RAS to renal injury induced by unilateral ureteral obstruction.

Methods: We examined the impact of CD-specific deletion of PRR, CD-specific deletion of renin, and S1P (site-1 protease) inhibitor PF429242 treatment on renal fibrosis and inflammation and the indices of the intrarenal RAS in a mouse model of unilateral ureteral obstruction.

Soluble (pro)renin receptor treats metabolic syndrome in mice with diet-induced obesity via interaction with PPARγ.

The therapies available for management of obesity and associated conditions are limited, because they are often directed toward an individual component of metabolic syndrome and are associated with adverse effects. Here, we report the multifaceted therapeutic potential of histidine-tagged recombinant soluble (pro)renin receptor (sPRR), termed sPRR-His, in a mouse model of diet-induced obesity (DIO). In the DIO model, 2-week administration of sPRR-His lowered body weight and remarkably improved multiple metabolic parameters in the absence of fluid retention.

Soluble (pro)renin receptor as a potential therapy for diabetes insipidus.

The antidiuretic hormone vasopressin (VP) is produced by the hypothalamus and is stored and secreted from the posterior pituitary. VP acts via VP type 2 receptors (V2Rs) on the basolateral membrane of principal cells of the collecting duct (CD) to regulate fluid permeability. The VP-evoked endocrine pathway is essential in determining urine concentrating capability.

The soluble (Pro) renin receptor does not influence lithium-induced diabetes insipidus but does provoke beiging of white adipose tissue in mice.

Earlier we reported that the recombinant soluble (pro) renin receptor sPRR-His upregulates renal aquoporin-2 (AQP2) expression, and attenuates polyuria associated with nephrogenic diabetes insipidus (NDI) induced by vasopressin type 2 receptor (V2R) antagonism. Patients that receive lithium therapy develop polyuria associated NDI that might be secondary to downregulation of renal AQP2. We hypothesized that sPRR-His attenuates indices of NDI associated with lithium treatment.

Antidiuretic Action of Collecting Duct (Pro)Renin Receptor Downstream of Vasopressin and PGE2 Receptor EP4.

Within the kidney, the (pro)renin receptor (PRR) is predominantly expressed in the collecting duct (CD), particularly in intercalated cells, and it is regulated by the PGE receptor EP Notably, EP also controls urinary concentration through regulation of aquaporin 2 (AQP2). Here, we tested the hypothesis that sequential activation of EP and PRR determines AQP2 expression in the CD, thus mediating the antidiuretic action of vasopressin (AVP). Water deprivation (WD) elevated renal PRR expression and urinary soluble PRR excretion in rats.

Soluble (pro)renin receptor via β-catenin enhances urine concentration capability as a target of liver X receptor.

The extracellular domain of the (pro)renin receptor (PRR) is cleaved to produce a soluble (pro)renin receptor (sPRR) that is detected in biological fluid and elevated under certain pathological conditions. The present study was performed to define the antidiuretic action of sPRR and its potential interaction with liver X receptors (LXRs), which are known regulators of urine-concentrating capability. Water deprivation consistently elevated urinary sPRR excretion in mice and humans.

Activation of ENaC in collecting duct cells by prorenin and its receptor PRR: involvement of Nox4-derived hydrogen peroxide.

The collecting duct (CD) has been recognized as an important source of prorenin/renin, and it also expresses (pro)renin receptor (PRR). The goal of this study was to examine the hypothesis that prorenin or renin via PRR regulates epithelial Na(+) channel (ENaC) activity in mpkCCD cells. Transepithelial Na(+) transport was measured by using a conventional epithelial volt-ohmmeter and was expressed as the calculated equivalent current (Ieq).

mPGES-2 deletion remarkably enhances liver injury in streptozotocin-treated mice via induction of GLUT2.

Background & Aims: Microsomal prostaglandin E synthase-2 (mPGES-2) deletion does not influence in vivo PGE2 production and the function of this enzyme remains elusive. The present study was undertaken to investigate the role of mPGES-2 in streptozotocin (STZ)-induced type-1 diabetes and organ injuries.

Methods: mPGES-2 wild type (WT) and knockout (KO) mice were treated by a single intraperitoneal injection of STZ at the dose of 120 mg/kg to induce type-1 diabetes.

Increased susceptibility of db/db mice to rosiglitazone-induced plasma volume expansion: role of dysregulation of renal water transporters.

Thiazolidinediones (TZDs), which are synthetic peroxisome proliferator-activated receptor subtype-γ (PPARγ), agonists are highly effective for treatment of type 2 diabetes. However, the side effect of fluid retention has significantly limited their application. Most of the previous studies addressing TZD-induced fluid retention employed healthy animals.