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Here, we demonstrated that plasma growth differentiation factor 15 (GDF15) is elevated across diverse fibrotic lung disease subtypes and correlates with markers of elevated right heart pressures but not pulmonary function indices, indicating a possible link to endothelial cell dysfunction. To investigate the import of endothelial GDF15 as a modifier of lung fibrosis pathogenesis, we generated endothelial cell\u2013specific\n                    <jats:italic>Gdf15<\/jats:italic>\n                    -KO mice, which showed protection from bleomycin-induced lung injury and fibrosis, with preserved lung function. RNA-seq of human pulmonary microvascular endothelial cells revealed altered expression of barrier-regulatory genes in\n                    <jats:italic>GDF15<\/jats:italic>\n                    -deficient endothelial cells compared with controls. Functional studies confirmed that\n                    <jats:italic>GDF15<\/jats:italic>\n                    knockdown attenuates thrombin-induced barrier disruption by reducing cytosolic Ca\n                    <jats:sup>2+<\/jats:sup>\n                    responses. Together, these findings implicate endothelial GDF15 as a modifier of vascular permeability and Ca\n                    <jats:sup>2+<\/jats:sup>\n                    signaling and a contributor to lung injury and fibrosis.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.200198","type":"journal-article","created":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T16:00:16Z","timestamp":1776960016000},"source":"Crossref","is-referenced-by-count":1,"title":["Endothelial GDF15 deficiency enhances barrier function and mitigates pulmonary fibrosis"],"prefix":"10.1172","volume":"11","author":[{"given":"Kristen","family":"Raffensperger","sequence":"first","affiliation":[{"name":"Pulmonary and Critical Care Medicine, UPMC, Pittsburgh, Pennsylvania, USA."},{"name":"Division of Pulmonary, Allergy, Critical Care, and Sleep Medicine, Department of 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