{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T15:14:54Z","timestamp":1783523694514,"version":"3.55.0"},"reference-count":30,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2025,6,10]],"date-time":"2025-06-10T00:00:00Z","timestamp":1749513600000},"content-version":"vor","delay-in-days":9,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Cellular Biochemistry"],"published-print":{"date-parts":[[2025,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    DNA damage is one of the key processes that underlie hepatic fibrosis, and its progression could lead to the development of neoplastic events and ultimately hepatocarcinoma. Tissue injury, including DNA damage, can involve the activation of purinergic signaling. It has been shown that P2Y2 receptor signaling is exacerbated during hepatic fibrosis. Little is known, however, about the roles played by P2Y2 receptor in the processes involved in fibrosis. In this study, we used CCl\n                    <jats:sub>4<\/jats:sub>\n                    treatment to induce a reversible hepatic fibrosis, and by using a microarray assay we observed an upregulation of transcripts related to the DNA damage repair of double strand breaks (DNA\u2010dr\u2010dsb) after P2Y2 receptor stimulation in primary cultures of hepatocytes from fibrotic mice. The transcriptional data were confirmed demonstrating an UTP\u2010promoted reduction in the number of \u03b3H2AX+ positive cells in etoposide\u2010treated fibrotic primary hepatocytes. Furthermore, HIF\u20101\u03b1, a known transcription factor that drives P2Y2 receptor expression, showed a significant increase upon CCl\n                    <jats:sub>4<\/jats:sub>\n                    treatment, especially within the perivascular zones. Chemical activation of HIF\u20101\u03b1 by CoCl\n                    <jats:sub>2<\/jats:sub>\n                    in fibrotic hepatocytes promoted a partial protection against increased levels of \u03b3H2AX induced by etoposide, as well as an evident enhancement in the intracellular calcium response induced by UTP in fibrotic hepatocytes, suggesting a regulatory role of this transcriptional factor on the effect of P2Y2 receptor on DNA\u2010dr\u2010dbs response. This regulation was also investigated pharmacologically by activating or blocking the signaling from either P2Y2 receptor or HIF\u20101\u03b1. Our work, in summary, shows a novel relationship between P2Y2 receptor\u2010dependent purinergic signaling and DNA\u2010dr\u2010dbs in hepatic fibrosis.\n                  <\/jats:p>","DOI":"10.1002\/jcb.70042","type":"journal-article","created":{"date-parts":[[2025,6,11]],"date-time":"2025-06-11T02:34:19Z","timestamp":1749609259000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Purinergic Receptor P2Y2 Activity Prevents DNA Damage in CCl\n                    <sub>4<\/sub>\n                    \u2010Induced Hepatic Fibrosis"],"prefix":"10.1002","volume":"126","author":[{"given":"Erandi","family":"Vel\u00e1zquez\u2010Miranda","sequence":"first","affiliation":[{"name":"Departamento de Neurobiolog\u00eda Celular y Molecular, Instituto de Neurobiolog\u00eda Universidad Nacional Aut\u00f3noma de M\u00e9xico Quer\u00e9taro M\u00e9xico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana Patricia","family":"Ju\u00e1rez\u2010Mercado","sequence":"additional","affiliation":[{"name":"Departamento de Neurobiolog\u00eda Celular y Molecular, Instituto de Neurobiolog\u00eda Universidad Nacional Aut\u00f3noma de M\u00e9xico Quer\u00e9taro M\u00e9xico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esperanza","family":"Mata\u2010Mart\u00ednez","sequence":"additional","affiliation":[{"name":"Departamento de Biolog\u00eda Celular y Desarrollo, Instituto de Fisiolog\u00eda Celular Universidad Nacional Aut\u00f3noma de M\u00e9xico CDMX M\u00e9xico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda Guadalupe","family":"Ram\u00edrez\u2010Ledesma","sequence":"additional","affiliation":[{"name":"Departamento de Neurobiolog\u00eda Celular y Molecular, Instituto de Neurobiolog\u00eda Universidad Nacional Aut\u00f3noma de M\u00e9xico Quer\u00e9taro M\u00e9xico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adriana","family":"Gonz\u00e1lez\u2010Gallardo","sequence":"additional","affiliation":[{"name":"Unidad de Proteogen\u00f3mica, Instituto de Neurobiolog\u00eda Universidad Nacional Aut\u00f3noma de M\u00e9xico Quer\u00e9taro M\u00e9xico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda Eugenia","family":"Ramos\u2010Aguilar","sequence":"additional","affiliation":[{"name":"Departamento de Neurobiolog\u00eda Celular y Molecular, Instituto de Neurobiolog\u00eda Universidad Nacional Aut\u00f3noma de M\u00e9xico Quer\u00e9taro M\u00e9xico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivia","family":"V\u00e1zquez\u2010Mart\u00ednez","sequence":"additional","affiliation":[{"name":"Departamento de Neurobiolog\u00eda Celular y Molecular, Instituto de Neurobiolog\u00eda Universidad Nacional Aut\u00f3noma de M\u00e9xico Quer\u00e9taro M\u00e9xico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9019-8246","authenticated-orcid":false,"given":"Mauricio","family":"D\u00edaz\u2010Mu\u00f1oz","sequence":"additional","affiliation":[{"name":"Departamento de Neurobiolog\u00eda Celular y Molecular, Instituto de Neurobiolog\u00eda Universidad Nacional Aut\u00f3noma de M\u00e9xico Quer\u00e9taro M\u00e9xico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8248-332X","authenticated-orcid":false,"given":"Francisco G.","family":"V\u00e1zquez\u2010Cuevas","sequence":"additional","affiliation":[{"name":"Departamento de Neurobiolog\u00eda Celular y Molecular, Instituto de Neurobiolog\u00eda Universidad Nacional Aut\u00f3noma de M\u00e9xico Quer\u00e9taro M\u00e9xico"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,6,10]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells9040875"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1124\/pr.110.003129"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.15005"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11302-016-9514-7"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2020.114361"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1124\/pr.58.3.3"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2020.114385"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-immunol-061020-053734"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00092.2014"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-19-1909"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.dnarep.2012.05.005"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.dnarep.2010.05.005"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1177\/0300060516662135"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11302-016-9532-5"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbagrm.2023.194963"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21072305"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1053\/jhep.2001.27949"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.26104"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gks402"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkp416"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1186\/gb-2007-8-1-r3"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M112.386599"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tranon.2021.101169"},{"key":"e_1_2_10_25_1","first-page":"43","article-title":"Inhibition of Myeloperoxidase Activity Have Impact on the Formation of DNA Double\u2010Strand Breaks Induced by Etoposide in HL\u201060 Cell Line","volume":"55","author":"Papie\u017c M. A.","year":"2015","journal-title":"Folia Medica Cracoviensia"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.3390\/ph16070944"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.21037\/atm-21-4222"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.2002.tb04680.x"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jss.2024.07.046"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11302-022-09900-3"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11302-016-9508-5"}],"container-title":["Journal of Cellular Biochemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcb.70042","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,30]],"date-time":"2025-11-30T12:41:27Z","timestamp":1764506487000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jcb.70042"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6]]},"references-count":30,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2025,6]]}},"alternative-id":["10.1002\/jcb.70042"],"URL":"https:\/\/doi.org\/10.1002\/jcb.70042","archive":["Portico"],"relation":{},"ISSN":["0730-2312","1097-4644"],"issn-type":[{"value":"0730-2312","type":"print"},{"value":"1097-4644","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6]]},"assertion":[{"value":"2025-01-27","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-05-30","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-06-10","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70042"}}