Unique Role of Proximal Tubule Dipeptidyl Peptidase 4 on Blood Pressure, Renal Sodium Handling, and Na⁺/H⁺ Exchanger Isoform 3 Phosphorylation.

ABSTRACT:

Background

Dipeptidyl peptidase 4 (DPP4) is a transmembrane serine exopeptidase highly expressed in the proximal tubule (PT). While its enzymatic role is well characterized, its non-enzymatic functions remain unclear. DPP4 physically associates with the Na⁺/H⁺ exchanger isoform 3 (NHE3), and DPP4 inhibitors promote natriuresis; however, the mechanisms by which DPP4 regulates NHE3 and its role in blood pressure (BP) regulation remain controversial. We hypothesized that PT DPP4 promotes sodium reabsorption and attenuates pressure-natriuresis by preventing NHE3 phosphorylation at serine 552 (pS552).

Methods

We generated PT-specific Dpp4 knockout mice (Dpp4^ΔPT) and examined the effects of PT-specific and global Dpp4 deletion (Dpp4^-/-)

SUBMITTER: Martins FL 

PROVIDER: S-EPMC12598389 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature