Renal release of yV-acetyl-seiyl-aspartyl-lysyl-proline is part of an antiflbrotic peptidergic system in the kidney

摘要

The antiflbrotic peptide N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP) is released from thymosin-p4 (Tp4) by Ihe meprin-a and prolyl oligopeptidase (POP) enzymes and is hydrolyzed by angioten-sin-converting enzyme (ACE). Ac-SDKP is present in urine; however, it is not clear whether de novo tubular release occurs or if glomerular filtration is the main source. We hypothesized that Ac-SDKP is released into the lumen of the nephrons and that it exerts an antifibrotic effect. We determined the presence of Tp4, meprin-a, and POP in the kidneys of Sprague-Dawley rats. The stop-flow technique was used to evaluate Ac-SDKP formation in different nephron segments. Finally, we decreased Ac-SDKP formation by inhibiting the POP enzyme and evaluated the long-term effect in renal fibrosis.