Targeting Hypoxia-Inducible Factor-1α/Pyruvate Dehydrogenase Kinase 1 Axis by Dichloroacetate Suppresses Bleomycin-induced Pulmonary Fibrosis
Goodwin J, Choi H, Hsieh MH, Neugent ML, Ahn JM, Hayenga HN, Singh PK, Shackelford DB, Lee IK, Shulaev V, Dhar S, Takeda N, Kim JW. Targeting Hypoxia-Inducible Factor-1α/Pyruvate Dehydrogenase Kinase 1 Axis by Dichloroacetate Suppresses Bleomycin-induced Pulmonary Fibrosis. American Journal Of Respiratory Cell And Molecular Biology 2017, 58: 216-231. PMID: 28915065, PMCID: PMC5805994, DOI: 10.1165/rcmb.2016-0186oc.Peer-Reviewed Original ResearchConceptsPyruvate dehydrogenase kinase 1Myofibroblast differentiationPulmonary fibrosisFibrotic progressionHIF-1αGlycolytic metabolismDehydrogenase kinase 1Knockout mouse modelHypoxia-inducible factorMetabolic reprogrammingCellular metabolismPotential therapeutic strategyKinase 1Glycolytic switchGenomic deletionsSustained activationMicroenvironmental influencesPreclinical efficacyGlycolytic reprogrammingPharmacological inhibitionReprogrammingMouse modelDifferentiationPharmacological approachesTherapeutic strategies