Fatty Acid Oxidation-Glycolysis Metabolic Transition Affects ECM Homeostasis in Silica-Induced Pulmonary Fibrosis.

ABSTRACT: Silicosis is a fatal occupational pulmonary disease that is characterized by irreversible replacement of lung parenchyma by aberrant Exracellular matrix (ECM). Metabolic reprogramming is a crucial mechanism for fibrosis. However, how the metabolic rewiring shifts the ECM homeostasis toward overaccumulation remains unclear. Herein, a phenotype with reduction in fatty acid oxidation (FAO) but enhanced glycolysis in myofibroblasts is shown. Perturbation of the glycolytic and FAO pathways, respectively, reveals distinct roles in the metabolic distribution of ECM deposition and degradation. Suppressed glycolysis leads to a decrease in insoluble ECM, primarily due to the inhibition of ECM-modifying enzyme activity and a decrease in glycine synthesis. Notably, promoted FAO facilitates the intrace

SUBMITTER: Sun W 

PROVIDER: S-EPMC11831484 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature