biostudies-literatureBao GYunnan Provincial Fund for High-Level Reserve Talents in Health ScienceYunnan Applied Basic Research Projects-Kunming Medical University Union FoundationNational Natural Science Foundation of China279https://www.ebi.ac.uk/biostudies/studies/S-EPMC12366207biostudies-literatureUnknown31(1)<h4>Background</h4>Disruption in bile duct barrier function contributes to hepatocyte toxicity in ischemia-reperfusion injury, often leading to surgical complications in liver resection, transplantation, and hemorrhagic shock. However, the underlying mechanisms remain incompletely understood.<h4>Methods</h4>Transcriptomic and proteomic analyses were conducted to examine tryptophan (Trp) metabolism in a Pringle maneuver-induced bile duct injury rat model; Hypoxia/Reoxygenation (H/R) was used to establish an in vitro cholangiocyte injury model. Cholangiocyte injury was assessed via hematoxylin and eosin (H&E) staining, Ki67/myeloperoxidase (MPO) immunohistochemistry, transmission electron microscopy (TEM), and TUNEL/CK19 co-staining. Tight junction integrity was evaluated by measuring transeMolecular medicine (Cambridge, Mass.)Kynu inhibition mitigates bile duct ischemic injury by rewiring tryptophan metabolism to restore tight junction integrity.PMC12366207202001AY070001-04081860121H-2018068Bao GBi PYang BZhang SYe ZLuo DfalseKynu inhibition mitigates bile duct ischemic injury by rewiring tryptophan metabolism to restore tight junction integrity.<h4>Background</h4>Disruption in bile duct barrier function contributes to hepatocyte toxicity in ischemia-reperfusion injury, often leading to surgical complications in liver resection, transplantation, and hemorrhagic shock. However, the underlying mechanisms remain incompletely understood.<h4>Methods</h4>Transcriptomic and proteomic analyses were conducted to examine tryptophan (Trp) metabolism in a Pringle maneuver-induced bile duct injury rat model; Hypoxia/Reoxygenation (H/R) was used to establish an in vitro cholangiocyte injury model. Cholangiocyte injury was assessed via hematoxylin and eosin (H&E) staining, Ki67/myeloperoxidase (MPO) immunohistochemistry, transmission electron microscopy (TEM), and TUNEL/CK19 co-staining. Tight junction integrity was evaluated by measuring transe2025-01-01T00:00:00Z2025 Aug2026-05-05T18:04:56.18Z2026-04-07T21:43:47.947ZS-EPMC123662074083042410.1186/s10020-025-01310-6