Prevention of sepsis-induced renal proximal tubular cell injury: prostaglandin uptake transporter PGT as a therapeutic target
(IAP-RP-HC25003)

Principal investigators: Ana Belén Fernández Martínez and Miguel Pita Dominguez, departamento de Biología, Universidad Autónoma de Madrid.

Project Summary
This project investigates the role of the prostaglandin transporter (PGT) and intracellular prostaglandin E2 (iPGE2) in proximal tubular epithelial cell injury associated with sepsis-induced acute kidney injury (AKI). Results obtained in different in vitro models, including HK-2 cells exposed to inflammatory mediators and cells incubated with plasma from patients with sepsis-associated AKI, indicate that activation of the PGT/iPGE2 axis contributes to tubular cell injury, whereas its pharmacological inhibition reduces cell death, cell detachment, cytoskeletal and tight-junction alterations, and increased paracellular permeability. These findings support the hypothesis that PGT may represent a novel therapeutic target for preventing or reducing sepsis-associated kidney injury.

As the next stage of the project, these findings will be validated in a murine model of sepsis induced by cecal ligation and puncture, assessing the potential nephroprotective effect of bromosulfophthalein, a PGT inhibitor, and thereby advancing the preclinical validation of this therapeutic strategy.