ArticleAmerican journal of respiratory and critical care medicine2012
Lactic acid is elevated in idiopathic pulmonary fibrosis and induces myofibroblast differentiation via pH-dependent activation of transforming growth factor-β.
Article in American journal of respiratory and critical care medicine, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 249 papers, 1 of them a synthesis that pooled it.
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Who cites it
249 citing papers in PubMed, 1 synthesis or guideline pooled it, 396 citations in OpenAlex.
- Genetic liability of gut microbiota for idiopathic pulmonary fibrosis and lung function: a two-sample Mendelian randomization study.Frontiers in cellular and infection microbiology · 2024Pooled it
- Lactate-induced MBD2 K186 lactylation promotes YAP1-dependent myofibroblast-like remodeling of Müller cells in diabetic retinopathy.Molecular biomedicine · 2026Article
- Silica Promotes Silicosis via the ROS/NF-κB p65 Signaling-Activated Hypoxia-Lactate Axis in Rats.Journal of applied toxicology : JAT · 2026Article
- Lactylation at the metabolic-epigenetic interface in cardiovascular diseases: context-dependent mechanisms and translational roadmap.Journal of advanced research · 2026Review
- Advances in metabolic reprogramming of pulmonary fibrosis.Chinese medical journal pulmonary and critical care medicine · 2026Review
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- Sirt5 preserves mitochondrial homeostasis to improve cardiac function in ischemia-reperfusion injury by inhibiting ANT2 lysine lactylation modification.Cellular and molecular life sciences : CMLS · 2026Article
- Multi-Omics and Machine Learning-Based Characterization of the Lactylation Microenvironment and Biomarker Identification in Crohn's Disease Intestinal Fibrosis.International journal of molecular sciences · 2026Article
- TGF-β coordinates alanine synthesis and import for myofibroblast differentiation in pulmonary fibrosis.JCI insight · 2026Article
- Kat5 deficiency in alveolar type II cells licenses STAT6-driven glycolytic reprogramming and pulmonary fibrosis.Nature communications · 2026Article
- MCT4 mediates hypoxia-induced extracellular lactate release from IPF fibroblasts.American journal of respiratory cell and molecular biology · 2026Article
- Fueling the fire: metabolic dysfunction and senescence as drivers of lung aging and disease.Physiological reviews · 2026Review
- The pentose phosphate pathway contributes to excess lactate production in radiation-induced fibroblast to myofibroblast transdifferentiation.The Journal of biological chemistry · 2026Article
- Macropinocytosis inhibition attenuates profibrotic responses in lung fibroblasts and pulmonary fibrosis models.The Journal of clinical investigation · 2026Article
- Fibroblasts as regulators of lung immunity, repair and fibrosis.Nature reviews. Immunology · 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
- Enhanced fatty acid availability rewires fibroblasts metabolism and decreases collagen deposition in lung fibrosis.Cellular and molecular life sciences : CMLS · 2026Article
- Prolonged high-density culture with restricted medium renewal induces epithelial-like plasticity in apical papilla stem cells.Biomolecules & biomedicine · 2026Article
- CRYAB_K92 lactylation drives hypertrophy of the ligamentum flavum via an S100A16/RAGE-mediated glycolysis-fibrosis positive feedback loop.Communications biology · 2026Article
189 more citing papers are in PubMed but not listed here.
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Authors and funding
14 authors at 3 institutions in 1 country.
Funding
Abstract
rationaleIdiopathic pulmonary fibrosis (IPF) is a complex disease for which the pathogenesis is poorly understood. In this study, we identified lactic acid as a metabolite that is elevated in the lung tissue of patients with IPF.
objectivesThis study examines the effect of lactic acid on myofibroblast differentiation and pulmonary fibrosis.
methodsWe used metabolomic analysis to examine cellular metabolism in lung tissue from patients with IPF and determined the effects of lactic acid and lactate dehydrogenase-5 (LDH5) overexpression on myofibroblast differentiation and transforming growth factor (TGF)-β activation in vitro. MEASUREMENTS AND MAIN
resultsLactic acid concentrations from healthy and IPF lung tissue were determined by nuclear magnetic resonance spectroscopy; α-smooth muscle actin, calponin, and LDH5 expression were assessed by Western blot of cell culture lysates. Lactic acid and LDH5 were significantly elevated in IPF lung tissue compared with controls. Physiologic concentrations of lactic acid induced myofibroblast differentiation via activation of TGF-β. TGF-β induced expression of LDH5 via hypoxia-inducible factor 1α (HIF1α). Importantly, overexpression of both HIF1α and LDH5 in human lung fibroblasts induced myofibroblast differentiation and synergized with low-dose TGF-β to induce differentiation. Furthermore, inhibition of both HIF1α and LDH5 inhibited TGF-β-induced myofibroblast differentiation.
conclusionsWe have identified the metabolite lactic acid as an important mediator of myofibroblast differentiation via a pH-dependent activation of TGF-β. We propose that the metabolic milieu of the lung, and potentially other tissues, is an important driving force behind myofibroblast differentiation and potentially the initiation and progression of fibrotic disorders.
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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.