ArticleCell proliferation2024
Pyruvate kinase M2 regulates kidney fibrosis through pericyte glycolysis during the progression from acute kidney injury to chronic kidney disease.
Article in Cell proliferation, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 31 citations in OpenAlex.
- Metabolic memory in the kidney: how lactate and lactylation drive the path from acute injury to chronic disease.Renal failure · 2026Review
- Mitochondrial dysfunction of renal tubular epithelial cells in chronic kidney disease-associated fibrosis: from organelle homeostasis to multicellular remodeling.Molecular biology reports · 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
- circCACNA1D drives pulmonary fibrosis by regulating pyruvate kinase M2 dimer‑tetramer switching.International journal of molecular medicine · 2026Article
- The Lactate-lactylation circuitry in kidney fibrosis: cellular crosstalk from tubular metabolic reprogramming to macrophage effector functions.Seminars in immunopathology · 2026Review
- Glucose Transporter 1 in Health and Disease.MedComm · 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
- Lactate and lactylation: mechanisms, function, diseases, and therapeutic targets.Molecular biomedicine · 2026Review
- Lactylation-mitochondria axis in chronic kidney disease: metabolic reprogramming, epigenetic dysregulation, and therapeutic potential.Molecular and cellular biochemistry · 2026Review
- The glycolytic enzyme PFKM promotes renal fibrosis by activating the NF-κB pathway via lactate-mediated H3K18 lactylation.Cellular and molecular life sciences : CMLS · 2026Article
- The double-edged sword effect of estrogen in kidney disease and its precision modulation.Frontiers in endocrinology · 2026Review
- Role of the TGF‑β/Smad signaling pathway in the transition from acute kidney injury to chronic kidney disease (Review).International journal of molecular medicine · 2025Review
- Lactate and Lactylation in AKI-to-CKD: Epigenetic Regulation and Therapeutic Opportunities.Cell proliferation · 2025Review
- Renal tubular epithelial IGFBP7 interacts with PKM2 to drive renal lipid accumulation and fibrosis.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Lactate and lactylation in the kidneys: Current advances and prospects (Review).International journal of molecular medicine · 2025Review
- Novel molecular mechanisms of immune evasion in hepatocellular carcinoma: NSUN2-mediated increase of SOAT2 RNA methylation.Cancer communications (London, England) · 2025Article
- Bidirectional Role of Pericytes in Ischemic Stroke.Brain sciences · 2025Review
- Pyruvate kinase M2 modulates mitochondrial dynamics and EMT in alveolar epithelial cells during sepsis-associated pulmonary fibrosis.Journal of translational medicine · 2025Article
- Ankrd1 as a potential biomarker for the transition from acute kidney injury to chronic kidney disease.Scientific reports · 2025Article
- Metabolite pathway alterations identified by magnetic resonance metabolomics in a proximal tubular epithelial cell line treated with TGF-β1.Physiological reports · 2025Article
Corrections and comments
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Authors and funding
12 authors at 1 institution in 1 country.
Funding
Abstract
We aimed to investigate the role of renal pericyte pyruvate kinase M2 (PKM2) in the progression of acute kidney injury (AKI) to chronic kidney disease (CKD). The role of PKM2 in renal pericyte-myofibroblast transdifferentiation was investigated in an AKI-CKD mouse model. Platelet growth factor receptor beta (PDGFRβ)-iCreERT2; tdTomato mice were used for renal pericyte tracing. Western blotting and immunofluorescence staining were used to examine protein expression. An 5-ethynyl-2'-deoxyuridine assay was used to measure renal pericyte proliferation. A scratch cell migration assay was used to analyse cell migration. Seahorse experiments were used to examine glycolytic rates. Enzyme-linked immunoassay was used to measure pyruvate kinase enzymatic activity and lactate concentrations. The PKM2 nuclear translocation inhibitors Shikonin and TEPP-46 were used to alter pericyte transdifferentiation. In AKI-CKD, renal pericytes proliferated and transdifferentiated into myofibroblasts and PKM2 is highly expressed in renal pericytes. Shikonin and TEPP-46 inhibited pericyte proliferation, migration, and pericyte-myofibroblast transdifferentiation by reducing nuclear PKM2 entry. In the nucleus, PKM2 promoted downstream lactate dehydrogenase A (LDHA) and glucose transporter 1 (GLUT1) transcription, which are critical for glycolysis. Therefore, PKM2 regulates pericyte glycolytic and lactate production, which regulates renal pericyte-myofibroblast transdifferentiation. PKM2-regulated renal pericyte-myofibroblast transdifferentiation by regulating downstream LDHA and GLUT1 transcription and lactate production. Reducing nuclear PKM2 import can reduce renal pericytes-myofibroblasts transdifferentiation, providing new ideas for AKI-CKD treatment.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.