Faculty, Staff and Student Publications

Language

English

Publication Date

8-1-2025

Journal

American Journal of Physiology-Renal Physiology

DOI

10.1152/ajprenal.00138.2025

PMID

40602784

PMCID

PMC12501988

PubMedCentral® Posted Date

10-8-2025

PubMedCentral® Full Text Version

Author MSS

Abstract

Methylthioadenosine phosphorylase (MTAP) is a key enzyme in purine metabolism that may influence cellular responses to injury. We evaluated the effects of prophylactic MTAP inhibition in mouse models of ischemia-reperfusion and cisplatin-induced acute kidney injury (AKI). MTAP inhibition was confirmed by accumulation of methylthioadenosine (MTA). Treated mice showed reduced renal injury and decreased tubular damage. Transcriptomic analysis revealed protection from inflammatory and stress pathways, while maintaining oxidative phosphorylation, fatty acid metabolism, and epithelial integrity-related genes. Analysis of human single-cell RNA-seq data from the Kidney Precision Medicine Project indicated that MTAP is highly expressed in kidney injury marker-positive adaptive proximal tubule cells, which display both reparative and maladaptive features during AKI. These findings highlight MTAP as a potential therapeutic target for modulating injury responses in AKI.

Keywords

Animals, Acute Kidney Injury, Purine-Nucleoside Phosphorylase, Humans, Disease Models, Animal, Reperfusion Injury, Mice, Inbred C57BL, Male, Mice, Cisplatin, Enzyme Inhibitors, Kidney Tubules, Proximal, Acute kidney injury, Methylthioadenosine phosphorylase, Prophylactic treatment

Published Open-Access

yes

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