biostudies-literatureUnknown6(9)Liu XAcute respiratory distress syndrome (ARDS) is a life-threatening condition affecting millions of people worldwide. The severity of ARDS is associated with the dysfunction of pulmonary endothelial cells (PECs). Metabolic reprogramming is characterized by enhanced glycolysis and lactate accumulation, which play a critical role in this process. Here, we showed that lactate levels in the lungs of patients with ARDS were associated with disease severity and prognosis. Lactate promoted PEC dysfunction and drove experimental ARDS progression via lysine lactylation (Klac), a recently described posttranslational modification. Suppression of lactate-induced lactylation mitigated the development of ARDS and inhibited the release of chemokines, particularly CXC motif chemokine ligand 12 (CXCL12), fromMedComme70344https://www.ebi.ac.uk/biostudies/studies/S-EPMC12394890biostudies-literatureGlobal Lactylome Reveals Lactylation-Dependent Mechanisms Underlying CXC Motif Chemokine Ligand 12 Expression in Pulmonary Endothelium During Acute Respiratory Distress Syndrome.PMC12394890Liu XDong XZheng MNi WWang HChang WfalseGlobal Lactylome Reveals Lactylation-Dependent Mechanisms Underlying CXC Motif Chemokine Ligand 12 Expression in Pulmonary Endothelium During Acute Respiratory Distress Syndrome.Acute respiratory distress syndrome (ARDS) is a life-threatening condition affecting millions of people worldwide. The severity of ARDS is associated with the dysfunction of pulmonary endothelial cells (PECs). Metabolic reprogramming is characterized by enhanced glycolysis and lactate accumulation, which play a critical role in this process. Here, we showed that lactate levels in the lungs of patients with ARDS were associated with disease severity and prognosis. Lactate promoted PEC dysfunction and drove experimental ARDS progression via lysine lactylation (Klac), a recently described posttranslational modification. Suppression of lactate-induced lactylation mitigated the development of ARDS and inhibited the release of chemokines, particularly CXC motif chemokine ligand 12 (CXCL12), from2025-01-01T00:00:00Z2025 Sep2026-05-29T19:08:20.752Z2026-05-18T03:07:40.524ZS-EPMC123948904089518710.1002/mco2.70344