ArticleSignal transduction and targeted therapy2022
Suppression of PFKFB3-driven glycolysis restrains endothelial-to-mesenchymal transition and fibrotic response.
Article in Signal transduction and targeted therapy, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 74 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
74 citing papers in PubMed, 102 citations in OpenAlex.
- Perioperative tislelizumab plus lenvatinib treatment for resectable hepatocellular carcinoma at high risk of recurrence: single-arm phase II trial.Nature communications · 2026Trial
- Catalytic lactate-regulatory nanosystems attenuate cellular senescence for atherosclerosis amelioration.Bioactive materials · 2026Article
- Iron, Copper, and Zinc Dyshomeostasis in Cardiovascular and Cerebrovascular Diseases: Redox Mechanisms, Evidence Levels, and Translational Prospects.International journal of molecular sciences · 2026Review
- Tubular PFKFB3 drives diabetic kidney fibrosis via lactate‑dependent H4K12 lactylation and HIPK2 transactivation.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
- The evolving landscape of the Warburg effect in gastric cancer: From molecular mechanisms to targeted therapy.Clinical and translational medicine · 2026Review
- Macrophage-to-Myofibroblast Transdifferentiation Contributes to Pulmonary Fibrosis via the MERTK-SPP1-SRC-TKS5 Signaling Axis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Lactylation in cardiac repair: Nexus and therapeutic opportunity.Journal of molecular and cellular cardiology plus · 2026Review
- P38γ drives aerobic glycolysis in liver sinusoidal endothelial cells and regulates alcoholic liver disease via the PFKFB3 signaling pathway.Molecular biology reports · 2026Article
- 6-Shogaol inhibits HSCs activation and liver fibrosis by regulating glycolytic reprogramming via targeting HIF-1α.Chinese medicine · 2026Article
- Environmental PET-microplastic exposure and risk of non-alcoholic fatty liver disease: An integrated computational toxicology and multi-omics study.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Dysregulation of the glycolysis-mitochondrial metabolism axis in osteoarthritis: mechanisms and therapeutic implications.Journal of orthopaedic translation · 2026Review
- Unraveling the fibrotic microenvironment in intrauterine adhesions through integrated metabolomics and proteomics.BMC women's health · 2026Article
- Single-cell multiomics uncovers an endothelial mechanosensitive PIEZO1-IL-33 axis driving pulmonary fibrosis.Nature communications · 2026Article
- Targeting Glycolytic Metabolism in Cancer Therapy: Current Approaches and Future Perspectives.Cells · 2026Review
- Design of RGD-functionalized GSH-responsive pegylated polymeric protacs for selective BRD4 degradation and EndMT-driven cardiac fibrosis inhibition.Journal of nanobiotechnology · 2026Article
- Glucose Metabolic Enzyme PFKFB3 in Cardiopulmonary Vascular Health and Disease.Circulation research · 2026Review
- Tubular NAT10 Promotes the Secretion of TGF-β and Lactate to Drive Fibroblast Activation in Diabetic Kidney Disease.International journal of biological sciences · 2026Article
- The role of lysine acylation in metabolic dysregulation and inflammatory responses within the hepatic immune microenvironment of MASLD.Frontiers in immunology · 2026Review
- Endothelial Metabolic Reprogramming Links Diabetes to Atherosclerosis.Diabetes, metabolic syndrome and obesity : targets and therapy · 2026Review
14 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Endothelial-to-mesenchymal transition (EndoMT), the process wherein endothelial cells lose endothelial identity and adopt mesenchymal-like phenotypes, constitutes a critical contributor to cardiac fibrosis. The phenotypic plasticity of endothelial cells can be intricately shaped by alteration of metabolic pathways, but how endothelial cells adjust cellular metabolism to drive EndoMT is incompletely understood. Here, we identified 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3) as a critical driver of EndoMT via triggering abnormal glycolysis and compromising mitochondrial respiration. Pharmacological suppression of PFKFB3 with salvianolic acid C (SAC), a phenolic compound derived from Salvia miltiorrhiza, attenuates EndoMT and fibrotic response. PFKFB3-haplodeficiency recapitulates the anti-EndoMT effect of SAC while PFKFB3-overexpression augments the magnitude of EndoMT and exacerbates cardiac fibrosis. Mechanistically, PFKFB3-driven glycolysis compromises cytoplasmic nicotinamide adenine dinucleotide phosphate (reduced form, NADPH) production via hijacking glucose flux from pentose phosphate pathway. Efflux of mitochondrial NADPH through isocitrate/α-ketoglutarate shuttle replenishes cytoplasmic NADPH pool but meanwhile impairs mitochondrial respiration by hampering mitochondrial iron-sulfur cluster biosynthesis. SAC disrupts PFKFB3 stability by accelerating its degradation and thus maintains metabolic homeostasis in endothelial cells, underlying its anti-EndoMT effects. These findings for the first time identify the critical role of PFKFB3 in triggering EndoMT by driving abnormal glycolysis in endothelial cells, and also highlight the therapeutic potential for pharmacological intervention of PFKFB3 (with SAC or other PFKFB3 inhibitors) to combat EndoMT-associated fibrotic responses via metabolic regulation.
Indexed as
Identifiers
What OpenQuestion holds
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.