ArticleCellular and molecular life sciences : CMLS2024
HSPA12A promotes c-Myc lactylation-mediated proliferation of tubular epithelial cells to facilitate renal functional recovery from kidney ischemia/reperfusion injury.
Article in Cellular and molecular life sciences : CMLS, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed.
- 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
- Lactylation: A central metabolic-epigenetic driver of sepsis-associated acute kidney injury.Molecular biology reports · 2026Review
- The Lactate-lactylation circuitry in kidney fibrosis: cellular crosstalk from tubular metabolic reprogramming to macrophage effector functions.Seminars in immunopathology · 2026Review
- Integrating Bulk and Single-Cell RNA Sequencing Identifies and Validates Lactylation-Related Signatures in Acute Kidney Injury.Biomedicines · 2026Article
- G6PC Downregulation Promotes Renal Calcium Oxalate Stone Formation via Lactate-Induced SNAIL1 K206 Lactylation and Epithelial-Mesenchymal Transition.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Endothelial SP1 lactylation promotes bronchopulmonary dysplasia via regulation of Cdkn1a expression.Scientific reports · 2026Article
- Targeting posttranslational modifications of oxidative stress pathways for the treatment of diabetic nephropathy.Journal of pharmaceutical analysis · 2026Review
- Lactylation and acetylation: parallel paths, divergent deeds, and research dilemmas.Journal of translational medicine · 2026Review
- Lactylation in pulmonary fibrosis: current understanding and challenges.Journal of translational medicine · 2026Review
- Lactate attenuates hepatic ischemia-reperfusion injury by reducing intrahepatic inflammation and suppressing hepatocyte-neutrophil interaction via the IL-33/ST2 pathway.Cell communication and signaling : CCS · 2026Article
- c-Myc: an emerging participant in heart failure.Frontiers in cardiovascular medicine · 2026Review
- Cellular senescence of renal tubular epithelial cells in diabetic kidney disease: emerging mechanisms and targeted interventions.Frontiers in cell and developmental biology · 2026Review
- Cordycepin ameliorates ischemia/reperfusion-induced acute kidney injury via inhibiting apoptosis and necroptosis.Iranian journal of basic medical sciences · 2026Article
- Lactylation Modification: From Basic Biological Process to Clinical Cardiovascular Diseases.Research (Washington, D.C.) · 2026Review
- Lactylation in kidney diseases: a review of regulatory mechanisms and therapeutic prospects.Frontiers in cell and developmental biology · 2026Review
- Lactylation modifications in urological diseases: molecular mechanisms and biological implications.Clinical epigenetics · 2025Review
- Lactate and lactylation in the kidneys: Current advances and prospects (Review).International journal of molecular medicine · 2025Review
- Lactate and lactylation in liver diseases: energy metabolism, inflammatory immunity and tumor microenvironment.Frontiers in immunology · 2025Review
- Lactylation in CNS disorders: mechanisms, cellular function, and disease relevance.Frontiers in cell and developmental biology · 2025Review
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Authors and funding
12 authors.
Funding
Abstract
Proliferation of renal tubular epithelial cells (TEC) is essential for restoring tubular integrity and thereby to support renal functional recovery from kidney ischemia/reperfusion (KI/R) injury. Activation of transcriptional factor c-Myc promotes TEC proliferation following KI/R; however, the mechanism regarding c-Myc activation in TEC is incompletely known. Heat shock protein A12A (HSPA12A) is an atypic member of HSP70 family. In this study, we found that KI/R decreased HSPA12A expression in mouse kidneys and TEC, while ablation of HSPA12A in mice impaired TEC proliferation and renal functional recovery following KI/R. Gain-of-functional studies demonstrated that HSPA12A promoted TEC proliferation upon hypoxia/reoxygenation (H/R) through directly interacting with c-Myc and enhancing its nuclear localization to upregulate expression of its target genes related to TEC proliferation. Notably, c-Myc was lactylated in TEC after H/R, and this lactylation was enhanced by HSPA12A overexpression. Importantly, inhibition of c-Myc lactylation attenuated the HSPA12A-induced increases of c-Myc nuclear localization, proliferation-related gene expression, and TEC proliferation. Further experiments revealed that HSPA12A promoted c-Myc lactylation via increasing the glycolysis-derived lactate generation in a Hif1α-dependent manner. The results unraveled a role of HSPA12A in promoting TEC proliferation and facilitating renal recovery following KI/R, and this role of HSPA12A was achieved through increasing lactylation-mediated c-Myc activation. Therefore, targeting HSPA12A in TEC might be a viable strategy to promote renal functional recovery from KI/R injury in patients.
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