Metabolic reprogramming in idiopathic pulmonary fibrosis

Abstract

Pulmonary fibrosis is caused by repeated damage to the pulmonary alveolar epithelium, leading to abnormal epithelial-mesenchymal transition and myofibroblast production, resulting in the accumulation of extra cellular matrix and remodeling of the interstitium. Analogous to many tumor cells, pulmonary fibrosis involves metabolic reprogramming, encompassing alterations in carbohydrate, lipid, and amino acid metabolism. Notably, this reprogramming is marked by enhanced glycolysis, diminished fatty acid oxidation paired with augmented synthesis, and increased degradation of glutamine. Glycolysis efficiently and rapidly fulfills the energy requirements for the proliferation of macrophages and fibroblasts during fibrotic development. Additionally, the reprogramming of amino acid metabolism in activated fibroblasts not only facilitates collagen synthesis but also intensifies myofibroblast activation by generating reactive oxygen species (ROS) during the production of hydroxyproline.

Keywords

• idiopathic pulmonary fibrosis|metabolic reprogramming|glycolysis|targeted therapy