RÉSUMÉ
Persistent enhancement of glycolysis in kidney tubular epithelial cells has been linked to the progression of chronic kidney disease, although the underlying mechanisms are largely unknown. In this issue of Kidney International, Wang et al. report that the glycolytic enzyme 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 plays a crucial role in kidney fibrosis by enhancing histone H4 lysine 12 lactylation through lactate accumulation. This increases the transcription of nuclear factor-κB-related genes and promotes inflammation and fibrosis. Inhibiting 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 reduces these effects, indicating therapeutic potential for kidney fibrosis.
Sujet(s)
Évolution de la maladie , Acide lactique , Insuffisance rénale chronique , Humains , Insuffisance rénale chronique/métabolisme , Insuffisance rénale chronique/anatomopathologie , Acide lactique/métabolisme , Animaux , Fibrose , Inflammation/métabolisme , Glycolyse , Histone/métabolisme , Facteur de transcription NF-kappa B/métabolisme , Rein/anatomopathologie , Rein/métabolismeRÉSUMÉ
Previous studies have indicated that succinate accumulation during kidney ischemia, and its oxidation during reperfusion, results in the production of excessive reactive oxygen species, mitochondrial dysfunction, and kidney injury. In this issue, Oh et al. have reported that pyruvate dehydrogenase kinase 4 (PDK4) inhibition in proximal tubules ameliorates kidney ischemia/reperfusion injury via suppressed succinate accumulation. This study suggests that PDK4 inhibition is a promising new treatment strategy for ischemic acute kidney injury.