ArticleThe Journal of clinical investigation2024
Postischemic inactivation of HIF prolyl hydroxylases in endothelium promotes maladaptive kidney repair by inducing glycolysis.
Article in The Journal of clinical investigation, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers, 1 of them a synthesis that pooled it.
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Who cites it
25 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Tetramethylpyrazine and renal ischemia-reperfusion injury: a systematic review and meta-analysis of preclinical studies.Frontiers in pharmacology · 2025Pooled it
- Advancements in early biomarkers of acute kidney injury: from traditional indicators to a paradigm shift in lactate metabolism.Annals of medicine · 2026Review
- Metabolic memory in the kidney: how lactate and lactylation drive the path from acute injury to chronic disease.Renal failure · 2026Review
- The lactate-lactylation axis in acute kidney injury: mechanisms from metabolic reprogramming to epigenetic regulation and clinical therapeutic prospects.International urology and nephrology · 2026Review
- Lactate-Mediated Lysine Lactylation in Renal Fibrosis: Current Progress and Challenges.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Review
- Twist Family BHLH Transcription Factor 1 orchestrates hypoxia-lactate crosstalk to bridge glycolytic flux and tubular maladaptation in fibrotic kidneys.Molecular biomedicine · 2026Article
- Article
- Single-cell RNA sequencing and spatial transcriptomics in the discovery of kidney disease potential biomarkers: a narrative review.BMC nephrology · 2026Review
- Hyperlactatemia in sepsis and shock: a renal metabolic perspective.Critical care (London, England) · 2026Review
- Glycolytic lactylation modulates cell death decisions in diabetic kidney disease: Metabolic‑epigenetic interplay between ferroptosis and autophagy in fibrotic remodeling (Review).International journal of molecular medicine · 2026Review
- Endothelial prolyl hydroxylase 3 mitigates maladaptive inflammation to promote post-ischemic kidney repair.Kidney international · 2026Article
- The endothelium response to kidney injury.Nature reviews. Nephrology · 2026Review
- Repurposing Syrosingopine for Cancer Therapy: Lactate Trapping and ISR Sensitization as Metabolic Vulnerabilities.Oncology and therapy · 2026Review
- Transition from acute kidney injury to chronic kidney disease: molecular mechanisms and therapeutic interventions.Molecular biomedicine · 2026Review
- Spatiotemporal Control of Intercellular Crosstalk: A New Therapeutic Paradigm for Halting Acute Kidney Injury to Chronic Kidney Disease Transition.Biomolecules · 2026Review
- Decoding organ fibrosis: mechanistic insights and emerging therapeutic strategies.Signal transduction and targeted therapy · 2026Review
- Article
- Lactate Metabolism and Protein Lactylation in Diabetic Kidney Disease: A Narrative Review.Diabetes, metabolic syndrome and obesity : targets and therapy · 2026Review
- Role of metabolic reprogramming and lactylation in diabetic nephropathy: molecular mechanisms and therapeutic prospects - a narrative review.Frontiers in endocrinology · 2026Review
- Kidney organoids as a novel platform to evaluate heat-stress-induced acute kidney injury pathogenesis.Bioengineering & translational medicine · 2026Article
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Abstract
Ischemic acute kidney injury (AKI) is common in hospitalized patients and increases the risk for chronic kidney disease (CKD). Impaired endothelial cell (EC) functions are thought to contribute in AKI to CKD transition, but the underlying mechanisms remain unclear. Here, we identify a critical role for endothelial oxygen sensing prolyl hydroxylase domain (PHD) enzymes 1-3 in regulating postischemic kidney repair. In renal endothelium, we observed compartment-specific differences in the expression of the 3 PHD isoforms in both mice and humans. Postischemic concurrent inactivation of endothelial PHD1, PHD2, and PHD3 but not PHD2 alone promoted maladaptive kidney repair characterized by exacerbated tissue injury, fibrosis, and inflammation. scRNA-Seq analysis of the postischemic endothelial PHD1, PHD2, and PHD3-deficient (PHDTiEC) kidney revealed an endothelial hypoxia and glycolysis-related gene signature, also observed in human kidneys with severe AKI. This metabolic program was coupled to upregulation of the SLC16A3 gene encoding the lactate exporter monocarboxylate transporter 4 (MCT4). Strikingly, treatment with the MCT4 inhibitor syrosingopine restored adaptive kidney repair in PHDTiEC mice. Mechanistically, MCT4 inhibition suppressed proinflammatory EC activation, reducing monocyte-EC interaction. Our findings suggest avenues for halting AKI to CKD transition based on selectively targeting the endothelial hypoxia-driven glycolysis/MCT4 axis.
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