Renal release of Ac-SDKP is part of an antifibrotic peptidergic system in the kidney.

Renal release of Ac-SDKP is part of an antifibrotic peptidergic system in the kidney. Am J Physiol Renal Physiol. 2018 Nov 07;: Authors: Romero CA, Kumar N, Nakagawa P, Worou ME, Liao TD, Peterson EL, Carretero OA Abstract The anti-fibrotic peptide Ac-SDKP is released from Thymosin β4 (Tβ4) by meprin-α and prolyl oligopeptidase (POP) enzymes and is hydrolyzed by angiotensin-converting enzyme (ACE). Ac-SDKP is present in urine however it is not clear if de novo tubular release exists or the glomerular filtration is the main source. We hypothesized that Ac-SDKP is released in the lumen of the nephron and that it has an anti-fibrotic effect. We determined the presence of Tβ4, meprin-α, 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. The precursor Tβ4, and the releasing enzymes meprin-α and POP were expressed in kidney. POP enzyme activity was almost double in the renal medulla compared to the renal cortex. Using the stop-flow technique, we detected the highest Ac-SDKP concentrations in the distal nephron. The infusion of a POP inhibitor into the kidney decreased the amount of Ac-SDKP in distal nephron segments and in the proximal nephron to a minor extent. An ACE inhibitor increased the Ac-SDKP content in all nephron ...
Source: Am J Physiol Renal P... - Category: Urology & Nephrology Authors: Tags: Am J Physiol Renal Physiol Source Type: research