MiR-199a-5p aggravates against renal ischemia-reperfusion and transplant injury by targeting AKAP1 to disrupt mitochondrial dynamics

This study identifies miR-199a-5p as a key regulator in renal ischemia-reperfusion injury through microRNA sequencing in mouse models and human delayed graft function. miR-199a-5p worsens renal IRI by aggravating graft dysfunction, tubular injury, and immune response, while its inhibition shows protective effects. miR-199a-5p downregulates A-kinase anchoring protein 1 (AKAP1), reducing dynamin-related protein 1 (Drp1)-s637 phosphorylation, increasing mitochondrial fission, and causing dysfunction. Targeting the miR-199a-5p/AKAP1/Drp1 axis offers therapeutic potential for renal IRI, as AKAP1 overexpression preserves mitochondrial integrity by maintaining Drp1-s637 phosphorylation.