Inhibition of methylthioadenosine phosphorylase provides protection from experimental acute kidney injury
Saliba, A.; Chen, Y.; Nelson, J. W.; Vetcha, A.; Wang, W. W.; Kang, L.; Ragi, N.; Maity, S.; Rabb, H.; Reeves, W. B.; Sharma, K.
Show abstract
Acute kidney injury (AKI) increases mortality risk and predisposes individuals to chronic kidney disease. Metabolic pathways play a crucial role in AKI pathophysiology. Here, we investigate the potential of methylthioadenosine phosphorylase (MTAP) inhibition as a novel renoprotective strategy in AKI. Using AKI mouse models, we demonstrate that a small molecule MTAP inhibitor significantly reduces kidney injury markers and improves renal histology. RNA sequencing reveals that MTAP inhibition modulates pathways associated with inflammation, oxidative phosphorylation, and cell survival. Additionally, analysis of human single-cell RNA sequencing data links MTAP expression to kidney injury marker in AKI. This study provides evidence of MTAP inhibition as a potential therapeutic strategy for AKI, highlighting metabolic dysregulation as a target for future clinical interventions.
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