ArticleAmerican journal of respiratory cell and molecular biology2018
Targeting Hypoxia-Inducible Factor-1α/Pyruvate Dehydrogenase Kinase 1 Axis by Dichloroacetate Suppresses Bleomycin-induced Pulmonary Fibrosis.
Article in American journal of respiratory cell and molecular biology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 96 papers, 1 of them a synthesis that pooled it.
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
96 citing papers in PubMed, 1 synthesis or guideline pooled it, 153 citations in OpenAlex.
- The Effect of Hypothermic Machine Perfusion to Ameliorate Ischemia-Reperfusion Injury in Donor Organs.Frontiers in immunology · 2022Pooled it
- Collagenase-Coated Polymeric Drug/siRNA Nanoparticles Overcome ECM and Regulate Metabolic Reprogramming of Fibroblasts for Alleviating Pulmonary Fibrosis.Small (Weinheim an der Bergstrasse, Germany) · 2026Article
- Antifibrotic Effects of Yi-Qi-Jian-Pi-Xiao-Yu Formula in Kidney via HIF1A-Driven M1 Macrophage Polarization.Phytochemical analysis : PCA · 2026Article
- MCT4 mediates hypoxia-induced extracellular lactate release from IPF fibroblasts.American journal of respiratory cell and molecular biology · 2026Article
- Metabolic reprogramming in fibrosis-related diseases: underlying mechanisms and therapeutics.Molecular biomedicine · 2026Review
- The metabolic code of pulmonary disease: from mechanisms to therapeutic opportunities.Breathe (Sheffield, England) · 2026Review
- Article
- Pathological Interplay of ROS With Myofibroblasts: An Impediment to Corneal Restitution.Oxidative medicine and cellular longevity · 2026Review
- Theranostic Nanoparticles in Prostate Cancer: Disrupting Hypoxia-Induced Glycolysis by Targeting Hypoxia-Inducible Factor-1 Alpha and Downstream Metabolites.Cancer medicine · 2026Review
- Aging and lung diseases: Unraveling mechanisms and therapeutic targets.Chinese medical journal pulmonary and critical care medicine · 2025Review
- Interplay of HIF-1α, SMAD2, and VEGF signaling in hypoxic renal environments: impact on macrophage polarization and renoprotection.Renal failure · 2025Article
- Glycolysis to lactylation: Unraveling the metabolic and epigenetic landscape in tissue fibrosis (Review).Molecular medicine reports · 2025Review
- PFKFB3 Promotes Myofibroblast Differentiation and Cardiac Fibrosis Through its Intra- and Extra- Cellular Roles.Journal of cardiovascular translational research · 2025Article
- Alternative Polyadenylation Contributes to Fibroblast Senescence in Pulmonary Fibrosis.Aging cell · 2025Article
- Article
- Dahuang Zhechong Pill Improves Pulmonary Fibrosis through miR-29b-2-5p/HK2 Mediated Glycolysis Pathway.Chinese journal of integrative medicine · 2025Article
- SRSF7 promotes pulmonary fibrosis through regulating PKM alternative splicing in lung fibroblasts.Acta pharmaceutica Sinica. B · 2025Article
- Melatonin attenuates inflammatory bone loss by alleviating mitophagy and lactate production.Apoptosis : an international journal on programmed cell death · 2025Article
- Decoding the complexity: mechanistic insights into comorbidities in idiopathic pulmonary fibrosis.The European respiratory journal · 2025Review
- Ablation of LRP6 in alpha-smooth muscle actin-expressing cells abrogates lung inflammation and fibrosis upon bleomycin-induced lung injury.FEBS letters · 2025Article
36 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
13 authors at 7 institutions in 3 countries.
Funding
Abstract
Hypoxia has long been implicated in the pathogenesis of fibrotic diseases. Aberrantly activated myofibroblasts are the primary pathological driver of fibrotic progression, yet how various microenvironmental influences, such as hypoxia, contribute to their sustained activation and differentiation is poorly understood. As a defining feature of hypoxia is its impact on cellular metabolism, we sought to investigate how hypoxia-induced metabolic reprogramming affects myofibroblast differentiation and fibrotic progression, and to test the preclinical efficacy of targeting glycolytic metabolism for the treatment of pulmonary fibrosis. Bleomycin-induced pulmonary fibrotic progression was evaluated in two independent, fibroblast-specific, promoter-driven, hypoxia-inducible factor (Hif) 1A knockout mouse models and in glycolytic inhibitor, dichloroacetate-treated mice. Genetic and pharmacological approaches were used to explicate the role of metabolic reprogramming in myofibroblast differentiation. Hypoxia significantly enhanced transforming growth factor-β-induced myofibroblast differentiation through HIF-1α, whereas overexpression of the critical HIF-1α-mediated glycolytic switch, pyruvate dehydrogenase kinase 1 (PDK1) was sufficient to activate glycolysis and potentiate myofibroblast differentiation, even in the absence of HIF-1α. Inhibition of the HIF-1α/PDK1 axis by genomic deletion of Hif1A or pharmacological inhibition of PDK1 significantly attenuated bleomycin-induced pulmonary fibrosis. Our findings suggest that HIF-1α/PDK1-mediated glycolytic reprogramming is a critical metabolic alteration that acts to promote myofibroblast differentiation and fibrotic progression, and demonstrate that targeting glycolytic metabolism may prove to be a potential therapeutic strategy for the treatment of pulmonary fibrosis.
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.