Abstract P286: (Pro)renin Receptor Mediates Inflammation Induced by Renal Injury

Abstract

(Pro)renin Receptor (PRR) expression in the kidney is reported to increase during injury from diabetic nephropathy, and ischemia. PRR is also reported to play a role in promoting renal inflammation. Aristolochic acid (AA) is a nephrotoxin which is known to target the proximal tubule. However, it is not known whether PRR plays a role in cortical inflammation caused by AA. We hypothesized that PRR promotes renal cortical inflammation in the setting of AA induced injury. This study utilized an inducible nephron specific PRR knockout (KO) mouse with KO induced at 6 weeks of age. Ten week old wild type and KO mice received intraperitoneal injection with 10mg/kg AA or vehicle. At baseline and two weeks after injection, glomerular filtration rate (GFR) was measured by FITC-sinistrin contrast injection. Two weeks after injection, kidneys were harvested, and RNA extracted from cortical tissue. PRR and IL-6 mRNA expression was measured by RT-PCR. Two weeks after injection, GFR was reduced in the Control +AA (1436 vs. 948 ul/min/100g body weight p<0.05) and KO + AA (1181 vs. 697 ul/min/100g body weight p<0.05) groups but not in control + vehicle group (1407 vs. 1186 ul/min/100g body weight). Renal cortical PRR expression increased by 157% in the Control + AA group compared to Control + vehicle (2.57 vs. 1) but was not increased in the KO + AA group (0.54). IL-6 expression similarly increased in the Control + AA group compared to Control + vehicle 1643% (16.43 vs. 1) and this response was attenuated in the KO compared to Control + vehicle (2.15 vs. 1). PRR promotes the inflammation of the renal cortex in response to AA injury. Further studies are needed to determine the long term role of PRR in renal injury.