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

Abstract

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. For example, a defect in any component of the VP signaling pathway can result in polyuria, polydipsia, and hypotonic urine, collectively termed diabetes insipidus (DI). A lack of VP production precipitates central diabetes insipidus (CDI) which can be managed effectively by VP supplementation. A majority of cases of nephrogenic diabetes insipidus (NDI) result from V2R mutations that impair receptor sensitivity. No specific therapy is currently available for management of NDI. Evidence is evolving that (Pro)renin receptor (PRR), a newly identified member of the renin-angiotensin system, is capable of regulating VP production and action. As such, PRR should be considered strongly as a therapeutic target for treating CDI and NDI. The current review will summarize recent advances in understanding the physiology of renal and central PRR as it relates to the two types of DI.

The Pathological Role of Pro(Renin) Receptor in Renal Inflammation

“… 32 , 55 Recent studies have identified a more specific role of sPRR in renal dysfunction which is demonstrated by the fact that sPRR activates the aquaporin 2 (AQP-2) channel in the distal nephron via frizzled-8 and β-catenin signaling pathway and increases water reabsorption. 11 , 56 Another study highlighted the role of sPRR in sodium reabsorption where sPRR upregulates epithelial sodium channel (ENaC) in the distal nephron and increases sodium reabsorption. 57 These findings indicate the role of sPRR in sodium and water homeostasis and the development of subsequent renal dysfunction.…”