Inhibiting 15-PGDH prevents ischemic renal injury by PGE2/EP4 signaling pathway mediating vasodilation, increased renal blood flow, and increased adenosine/A2A.

Inhibiting 15-PGDH prevents ischemic renal injury by PGE2/EP4 signaling pathway mediating vasodilation, increased renal blood flow, and increased adenosine/A2A. Am J Physiol Renal Physiol. 2020 Nov 02;: Authors: Kim HJ, Kim SH, Kim M, Baik H, Park SJ, Kang MS, Kim DH, Kim BW, Markowitz SD, Bae KB Abstract We demonstrate the marked activity of SW033291, an inhibitor of 15-hydoxyprostaglandin dehydrogenase (15-PGDH), in preventing acute kidney injury (AKI) in a murine model of ischemia reperfusion injury. AKI due to ischemic injury represents a significant clinical problem. Prostaglandin E2 (PGE2) is vasodilatory in the kidney, but is rapidly degraded in vivo due to catabolism by 15-PGDH. We investigated the potential of SW033291, a potent and specific 15-PGDH inhibitor, as prophylactic treatment for ischemic AKI. Prophylactic administration of SW033291 significantly increased renal tissue PGE2 levels and increased post-AKI renal blood flow and renal arteriole area. In parallel, prophylactic SW033291 decreased post-AKI renal morphology injury score and tubular apoptosis and markedly reduced biomarkers of renal injury that included BUN, creatinine, NGAL and KIM-1. Prophylactic SW033291 also reduced post-AKI induction of proinflammatory cytokines, high mobility group box 1 (HMGB1), and malondialdehyde (MDA). Protective effects of SW033291 were mediated by PGE2 signaling as they could be blocked by pharmacologic inhibition of PGE2 synthes...
Source: Am J Physiol Renal P... - Category: Urology & Nephrology Authors: Tags: Am J Physiol Renal Physiol Source Type: research