Advances in regulatory mechanisms of glycolysis in the pathological process of pulmonary fibrosis

Pulmonary fibrosis (PF) is a highly lethal and progressive interstitial lung disease, for which there is currently a lack of effective treatments capable of reversing the disease process. In recent years, the role of metabolic reprogramming in the pathogenesis of PF has garnered increasing attention, with glycolysis, as a core energy metabolism pathway, playing a pivotal role in the initiation and progression of PF. This review systematically summarizes the pathological functions of key glycolytic regulators—including TGF-β, HIF-1α, GLUT, lactate, HK, PFK-1, and PK—in pulmonary fibrosis. It further elucidates the mechanisms through which these factors influence core fibrotic processes such as fibroblast activation, myofibroblast differentiation, and extracellular matrix deposition by modulating glycolytic flux, metabolite production, and cellular energy status. Additionally, this article integrates and analyzes the crosstalk and synergistic effects among signaling pathways such as PI3K/Akt, TGF-β/Smad, mTOR, HIF-1α, and AMPK in the regulation of glycolysis, revealing their network-based regulatory roles in pulmonary fibrosis. This review aims to provide an in-depth analysis of the pathogenesis of pulmonary fibrosis from the perspective of glycolysis, offering a theoretical foundation and new research directions for therapeutic strategies targeting glycolysis and related signaling pathways.