{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T12:18:13Z","timestamp":1788265093666,"version":"build-2803163510"},"reference-count":124,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:p>\n                    Idiopathic pulmonary fibrosis (IPF) is a progressive, fatal interstitial lung disease characterized by usual interstitial pneumonia, relentless decline in lung function and incomplete disease modification by available antifibrotic therapies. Beyond canonical profibrotic pathways, accumulating evidence identifies aberrant glutamine metabolism as a convergent metabolic feature of IPF pathogenesis. In structural cells, glutaminolysis fuels myofibroblast activation,\n                    <jats:italic>de novo<\/jats:italic>\n                    glycine and proline synthesis for collagen, whereas epithelial glutamine utilization may support antioxidant defence, mitochondrial adaptation and repair. In immune cells, glutamine shapes macrophage and T-cell polarization and may contribute to an inflammatory, profibrotic microenvironment. Glutamine-derived intermediates intersect with mTOR\/AMPK and TGF-\n                    <jats:italic>\u03b2<\/jats:italic>\n                    \/Smad signalling and act as cofactors for epigenetic regulators, thereby stabilizing apoptosis-resistant, profibrotic transcriptional programmes. Experimental models and human studies further demonstrate upregulation of glutamine transporters and glutaminase 1 (GLS1) in fibrotic lungs, protection from bleomycin-induced fibrosis after genetic or pharmacologic GLS1 inhibition, and a genetic association between lower circulating glutamine and increased IPF risk. Importantly, the effects of glutamine metabolism are context- and cell type\u2013dependent: epithelial and immune glutamine utilization may support repair, barrier integrity and host defence, whereas excessive fibroblast-directed glutaminolysis promotes matrix accumulation. Building on these observations, this review synthesizes current knowledge on cell type\u2013relevant glutamine metabolism in lung fibrosis, distinguishes direct lung-fibrosis evidence from extrapolated mechanistic evidence, delineates its integration with fibrogenic signalling, oxidative stress, mitochondrial stress and immunometabolism, and critically evaluates the therapeutic potential and caveats of targeting glutamine uptake, catabolism and nutrient-sensing pathways as adjuncts to existing antifibrotic regimens.\n                  <\/jats:p>","DOI":"10.3389\/fonc.2026.1873614","type":"journal-article","created":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T11:45:05Z","timestamp":1788263105000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["The role of glutamine metabolism in the pathogenesis of idiopathic pulmonary fibrosis and its therapeutic 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