{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T10:32:32Z","timestamp":1785407552722,"version":"3.56.0"},"reference-count":144,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2026,7,5]],"date-time":"2026-07-05T00:00:00Z","timestamp":1783209600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003141","name":"Secretar\u00eda de Ciencia, Humanidades, Tecnolog\u00eda e Innovaci\u00f3n","doi-asserted-by":"publisher","award":["CBF-2023-2024-200"],"award-info":[{"award-number":["CBF-2023-2024-200"]}],"id":[{"id":"10.13039\/501100003141","id-type":"DOI","asserted-by":"publisher"}]},{"award":["CBF-2023-2024-200"],"award-info":[{"award-number":["CBF-2023-2024-200"]}],"id":[{"id":"https:\/\/ror.org\/059ex5q34","id-type":"ROR","asserted-by":"publisher"}]},{"name":"PAPIIT-UNAM","award":["IN204926"],"award-info":[{"award-number":["IN204926"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Fibrosis is a common extracellular matrix pathology characterized by increased scarring, representing a critical checkpoint toward cirrhosis and hepatocellular carcinoma. Its onset involves coordinated interplay among hepatocytes, Kupffer, and hepatic stellate cells (HSCs). Extracellular ATP and its derivates act as crucial damage-associated molecular patterns when released by injured liver cells, binding to specific purinergic receptors (P2X, P2Y, and P1) to establish an autocrine\u2013paracrine signaling loop. The hepatic fibrotic response underlies the activation of ATP receptors that generate second messengers and cationic conductance. In parallel, extracellular nucleotidases hydrolyze ATP towards less phosphorylated intermediates and adenosine. This review focuses on the role of P2X and P2Y receptors in liver injury. The P2X7 receptor regulates the NLRP3 inflammasome in Kupffer cells and HSCs, while the P2X4 receptor is upregulated in myofibroblasts, modulating migration and matrix synthesis. Among P2Y receptors, P2Y2 drives inflammation and steatosis but promotes HIF-1\u03b1-mediated DNA repair. The P2Y6 receptor promotes alcohol-induced injury but restrains metabolic-dysfunction-associated steatohepatitis. P2Y2 and P2Y4 receptors maintain biliary homeostasis in cholangiocytes, whereas the P2Y1 receptor preserves HSC quiescence by blocking YAP translocation. Finally, UDP-glucose\u2013P2Y14 induces HSC activation. Targeting these specific purinergic receptors or ecto-nucleotidases represents a promising pharmacological frontier against hepatic fibrosis.<\/jats:p>","DOI":"10.3390\/ijms27136030","type":"journal-article","created":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T13:43:14Z","timestamp":1783345394000},"page":"6030","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Liver Fibrosis and Purinergic Signaling: Autocrine\u2013Paracrine Role of ATP in Liver Damage"],"prefix":"10.3390","volume":"27","author":[{"given":"Blanca Ver\u00f3nica","family":"Ramos-Rosillo","sequence":"first","affiliation":[{"name":"Departamento de Neurobiolog\u00eda Celular y Molecular, Instituto de Neurobiolog\u00eda, Universidad Nacional Aut\u00f3noma de M\u00e9xico, Juriquilla, Quer\u00e9taro CP 76230, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0457-7558","authenticated-orcid":false,"given":"Esperanza","family":"Mata-Mart\u00ednez","sequence":"additional","affiliation":[{"name":"Departamento de Biolog\u00eda Celular, Instituto de Fisiolog\u00eda Celular, Universidad Nacional Aut\u00f3noma de M\u00e9xico, Ciudad de M\u00e9xico CP 04510, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9019-8246","authenticated-orcid":false,"given":"Mauricio","family":"D\u00edaz-Mu\u00f1oz","sequence":"additional","affiliation":[{"name":"Departamento de Neurobiolog\u00eda Celular y Molecular, Instituto de Neurobiolog\u00eda, Universidad Nacional Aut\u00f3noma de M\u00e9xico, Juriquilla, Quer\u00e9taro CP 76230, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francisco G.","family":"V\u00e1zquez-Cuevas","sequence":"additional","affiliation":[{"name":"Departamento de Neurobiolog\u00eda Celular y Molecular, Instituto de Neurobiolog\u00eda, Universidad Nacional Aut\u00f3noma de M\u00e9xico, Juriquilla, Quer\u00e9taro CP 76230, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1542","DOI":"10.1016\/j.jhep.2023.06.003","article-title":"A Multisociety Delphi Consensus Statement on New Fatty Liver Disease Nomenclature","volume":"79","author":"Rinella","year":"2023","journal-title":"J. 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