ArticleAmerican journal of respiratory cell and molecular biology2021
Lung Myofibroblasts Promote Macrophage Profibrotic Activity through Lactate-induced Histone Lactylation.
Article in American journal of respiratory cell and molecular biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 254 papers, 1 of them a synthesis that pooled it.
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Who cites it
254 citing papers in PubMed, 1 synthesis or guideline pooled it, 325 citations in OpenAlex.
- Pooled it
- Lactate-induced MBD2 K186 lactylation promotes YAP1-dependent myofibroblast-like remodeling of Müller cells in diabetic retinopathy.Molecular biomedicine · 2026Article
- An Acidic Tubulointerstitial Microenvironment Delays Cell-Cycle Progression in Proximal Tubule Cells and Fibroblasts and Synergizes With Lactate to Drive Phenotypic Alterations.Acta physiologica (Oxford, England) · 2026Article
- ACAT1-Mediated SP1-K694 Lactylation Promotes M1 Macrophage Polarization via TREM1 Transcription in COPD.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- 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
- Roles of lactate and protein lactylation in neurogenesis and neurodegenerative disease.Journal of translational medicine · 2026Review
- Advances in metabolic reprogramming of pulmonary fibrosis.Chinese medical journal pulmonary and critical care medicine · 2026Review
- Lactylation: A central metabolic-epigenetic driver of sepsis-associated acute kidney injury.Molecular biology reports · 2026Review
- Lactate metabolism and protein lactylation in inflammatory and tumor microenvironments.Molecular biomedicine · 2026Review
- The Lactate-lactylation circuitry in kidney fibrosis: cellular crosstalk from tubular metabolic reprogramming to macrophage effector functions.Seminars in immunopathology · 2026Review
- Targeting lactylation in hepatocellular carcinoma: Mechanistic insights and therapeutic opportunities (Review).International journal of molecular medicine · 2026Review
- Lysine l-Lactylation: Bridging Metabolism, Chromatin and Disease.Cell proliferation · 2026Review
- The landscape of protein post-translational modifications in the pathogenesis of acute respiratory distress syndrome.Journal of thoracic disease · 2026Review
- Acute-on-Chronic Liver Failure: An Eroded Cliff Hit by a Storm-A Narrative Review.International journal of molecular sciences · 2026Review
- Comparative Quantitative Profiling of Protein Lactylation Reveals a Dynamic Tissues-Specific Network Associated with Metabolic Specialization in Yaks.Animals : an open access journal from MDPI · 2026Article
- Convergent Microenvironment Linking Idiopathic Pulmonary Fibrosis and Lung Cancer.Expert reviews in molecular medicine · 2026Review
- Protein lactylation in health and diseases: molecular mechanisms, biological significance, and clinical implications.Signal transduction and targeted therapy · 2026Review
- Mitochondrial-endoplasmic reticulum interactions in lung diseases.Cell death & disease · 2026Review
- Training PBertKla on an Integrated Multi-Source Dataset with a Machine-Learning Layer for Lysine Lactylation Site Prediction.International journal of molecular sciences · 2026Article
- A Novel Approach to Neuropathic Pain Treatment: Lactylation Targeting Microglia.Molecular neurobiology · 2026Review
194 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
Abstract
Augmented glycolysis due to metabolic reprogramming in lung myofibroblasts is critical to their profibrotic phenotype. The primary glycolysis byproduct, lactate, is also secreted into the extracellular milieu, together with which myofibroblasts and macrophages form a spatially restricted site usually described as fibrotic niche. Therefore, we hypothesized that myofibroblast glycolysis might have a non-cell autonomous effect through lactate regulating the pathogenic phenotype of alveolar macrophages. Here, we demonstrated that there was a markedly increased lactate in the conditioned media of TGF-β1 (transforming growth factor-β1)-induced lung myofibroblasts and in the BAL fluids (BALFs) from mice with TGF-β1- or bleomycin-induced lung fibrosis. Importantly, the media and BALFs promoted profibrotic mediator expression in macrophages. Mechanistically, lactate induced histone lactylation in the promoters of the profibrotic genes in macrophages, consistent with the upregulation of this epigenetic modification in these cells in the fibrotic lungs. The lactate inductions of the histone lactylation and profibrotic gene expression were mediated by p300, as evidenced by their diminished concentrations in p300-knockdown macrophages. Collectively, our study establishes that in addition to protein, lipid, and nucleic acid molecules, a metabolite can also mediate intercellular regulations in the setting of lung fibrosis. Our findings shed new light on the mechanism underlying the key contribution of myofibroblast glycolysis to the pathogenesis of lung fibrosis.
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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.