{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T16:10:39Z","timestamp":1787242239466,"version":"build-2736575974"},"reference-count":104,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T00:00:00Z","timestamp":1768435200000},"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. Transplant."],"abstract":"<jats:p>\n                    Cholangiocytes\u2014the epithelial cells lining the biliary tree\u2014are especially vulnerable to ischemic injury, particularly in the setting of orthotopic liver transplantation (OLT). This susceptibility stems from their reliance on an arterial blood supply and limited anaerobic capacity, predisposing them to hypoxia-induced damage. While significant research has focused on hepatocellular ischemia-reperfusion injury (IRI), the specific biology of cholangiocyte injury and regeneration remains underexplored. Recent evidence highlights purinergic signaling as a key regulator\n                    <jats:italic>y<\/jats:italic>\n                    axis in the liver's response to ischemia. Upon hypoxic stress, extracellular ATP is released as a damage-associated molecular pattern (DAMP), activating pro-inflammatory P\n                    <jats:sub>2<\/jats:sub>\n                    receptors. Enzymatic degradation of ATP by CD39 and CD73 shifts the signaling balance toward adenosine, a potent anti-inflammatory and cytoprotective molecule acting through P\n                    <jats:sub>1<\/jats:sub>\n                    receptors (A\n                    <jats:sub>1<\/jats:sub>\n                    , A\n                    <jats:sub>2<\/jats:sub>\n                    A, A\n                    <jats:sub>2<\/jats:sub>\n                    B, A\n                    <jats:sub>3<\/jats:sub>\n                    ). This review synthesizes emerging data on purinergic signaling in cholangiocyte biology, emphasizing its role in modulating inflammatory injury, cellular crosstalk, and regeneration. We discuss how A\n                    <jats:sub>2<\/jats:sub>\n                    A and A\n                    <jats:sub>2<\/jats:sub>\n                    B receptor pathways suppress immune-mediated damage and promote cholangiocyte proliferation, with downstream effects on IL-6 secretion, vascular remodeling, and bile duct survival. As biliary complications remain a major cause of graft dysfunction post-transplant, harnessing purinergic mechanisms may offer a novel therapeutic frontier in improving cholangiocyte resilience and overall transplant outcomes.\n                  <\/jats:p>","DOI":"10.3389\/frtra.2025.1731982","type":"journal-article","created":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T06:24:45Z","timestamp":1768458285000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Purinergic signaling and cholangiocyte regeneration: a new frontier in ischemic liver injury"],"prefix":"10.3389","volume":"4","author":[{"given":"Chinedu","family":"Nwaduru","sequence":"first","affiliation":[{"name":"Division of Transplant and Advanced Hepatobiliary Surgery, The University of Utah","place":["Salt Lake, UT, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Onyekachi Emmanuel","family":"Anyagwa","sequence":"additional","affiliation":[{"name":"Department of Surgery, New Vision University","place":["Tbilisi, Georgia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Fenlon","sequence":"additional","affiliation":[{"name":"Division of Transplant and Advanced Hepatobiliary Surgery, The University of Utah","place":["Salt Lake, UT, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle","family":"Buff","sequence":"additional","affiliation":[{"name":"Division of Transplant and Advanced Hepatobiliary Surgery, The University of Utah","place":["Salt Lake, UT, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Motaz","family":"Selim","sequence":"additional","affiliation":[{"name":"Division of Transplant and Advanced Hepatobiliary Surgery, The University of Utah","place":["Salt Lake, UT, United 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