Abstract P239: (Pro)Renin Receptor Contributes to Albumin Overload Nephropathy: Role of Site-1 Protease-Derived Soluble (Pro) Renin Receptor [Session Title: Onsite Poster Competition I With Reception]

(Pro) renin receptor (PRR) is a new member of the renin-angiotensin system (RAS) and its role in chronic kidney disease largely remains elusive. We tested the role of PRR in albumin overload (OA) nephropathy. Uninephretomized Sprague-Dawley rats were treated for 7 weeks with vehicle, bovine serum albumin (BSA) (5 g/kg/d via a single i.p. injection) or in combination with PRO20 (500 μg/kg/d via i.p. 3 times a day). The OA rat exhibited severe proteinuria (23-fold), interstitial fibrosis, and oxidative stress, accompanied with increases in urinary renin activity (3.6-fold), urinary angiotensinogen (AGT, 3.6-fold), urinary AngII(7.8-fold), renal ACE mRNA (2.4-fold), all of which were significantly attenuated by PRO20. Urinary soluble PRR (sPRR) as assessed by ELISA was increased 13.6-fold in the OA model. In cultured HK-2 cells, BSA treatment for 24 h decreased full-length PRR (76% reduction) and increased sPRR (8-fold). BSA also increased medium renin activity (3.0-fold), IL6 (2.9-fold for mRNA and 4.1-fold for medium protein) and IL8 (5.5-fold for mRNA and 2.6-fold for medium protein), all of which were attenuated by PRO20 or PRR siRNA. Although furin or ADAM19 was previously shown to mediate the generation of sPRR, inhibition of either one of these had no effect on BSA-induced cleavage of PRR. In contrast, a serine protease inhibitor AEBSF significantly suppressed the production of sPRR. Of serine proteases, proprotein convertases (PCs) mediates post-translational processing...
Source: Hypertension - Category: Cardiology Authors: Tags: Poster Abstract Presentations Source Type: research