{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,1]],"date-time":"2026-03-01T12:23:09Z","timestamp":1772367789814,"version":"3.50.1"},"reference-count":73,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2019,12,14]],"date-time":"2019-12-14T00:00:00Z","timestamp":1576281600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100014440","name":"Ministerio de Ciencia, Innovaci\u00f3n y Universidades","doi-asserted-by":"publisher","award":["RTI2018-095114-B-I00"],"award-info":[{"award-number":["RTI2018-095114-B-I00"]}],"id":[{"id":"10.13039\/100014440","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Consejo Nacional de Ciencia y Tecnolog\u00eda (CONACYT), Fondo Sectorial de Investigaci\u00f3n para la Educaci\u00f3n","award":["257743"],"award-info":[{"award-number":["257743"]}]}],"content-domain":{"domain":["www.mdpi.com"],"crossmark-restriction":true},"short-container-title":["Cells"],"abstract":"<jats:p>We elucidate the relevance of fibroblast growth factor 15 (FGF15) in liver transplantation (LT) using rats with both steatotic and non-steatotic organs from donors after cardiocirculatory death (DCD). Compared to LT from non-DCDs, the induction of cardiocirculatory death (CD) increases hepatic damage, proliferation, and intestinal and circulatory FGF15. This is associated with high levels of FGF15, bilirubin and bile acids (BAs), and overexpression of the enzyme involved in the alternative BA synthesis pathway, CYP27A1, in non-steatotic livers. Furthermore, CD activates the proliferative pathway, Hippo\/YAP, in these types of liver. Blocking FGF15 action in LT from DCDs does not affect CYP27A1 but causes an overexpression of CYP7A, an enzyme from the classic BA synthesis pathway, and this is related to further accumulation of BAs and exacerbated damage. FGF15 inhibition also impairs proliferation without changing Hippo\/YAP. In spite of worse damage, steatosis prevents a proliferative response in livers from DCDs. In steatotic grafts, CD does not modify CYP7A1, CYP27A1, BA, or the Hippo\/YAP pathway, and FGF15 is not involved in damage or proliferation. Thus, endogenous FGF15 protects against BA accumulation and damage and promotes regeneration independently of the Hippo\/YAP pathway, in non-steatotic LT from DCDs. Herein we show a minor role of FGF15 in steatotic LT from DCDs.<\/jats:p>","DOI":"10.3390\/cells8121640","type":"journal-article","created":{"date-parts":[[2019,12,16]],"date-time":"2019-12-16T05:19:38Z","timestamp":1576473578000},"page":"1640","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["The Effect of Fibroblast Growth Factor 15 Signaling in Non-Steatotic and Steatotic Liver Transplantation from Cardiocirculatory Death"],"prefix":"10.3390","volume":"8","author":[{"given":"Cindy G.","family":"Avalos-de Le\u00f3n","sequence":"first","affiliation":[{"name":"Institut d\u2019Investigacions Biom\u00e8diques August Pi I Sunyer (IDIBAPS), 08036 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5890-1042","authenticated-orcid":false,"given":"M\u00f3nica B.","family":"Jim\u00e9nez-Castro","sequence":"additional","affiliation":[{"name":"Institut d\u2019Investigacions Biom\u00e8diques August Pi I Sunyer (IDIBAPS), 08036 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1623-8131","authenticated-orcid":false,"given":"Mar\u00eda Eugenia","family":"Cornide-Petronio","sequence":"additional","affiliation":[{"name":"Institut d\u2019Investigacions Biom\u00e8diques August Pi I Sunyer (IDIBAPS), 08036 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8862-7104","authenticated-orcid":false,"given":"Jos\u00e9","family":"Gulfo","sequence":"additional","affiliation":[{"name":"Institut d\u2019Investigacions Biom\u00e8diques August Pi I Sunyer (IDIBAPS), 08036 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0688-6856","authenticated-orcid":false,"given":"Floriana","family":"Rotondo","sequence":"additional","affiliation":[{"name":"Institut d\u2019Investigacions Biom\u00e8diques August Pi I Sunyer (IDIBAPS), 08036 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7736-4089","authenticated-orcid":false,"given":"Jordi","family":"Gracia-Sancho","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Hep\u00e1ticas y Digestivas (CIBERehd), 08036 Barcelona, Spain"},{"name":"Liver Vascular Biology Research Group, IDIBAPS, 08036 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7533-1478","authenticated-orcid":false,"given":"Aran\u00ed","family":"Casillas-Ram\u00edrez","sequence":"additional","affiliation":[{"name":"Hospital Regional de Alta Especialidad de Ciudad Victoria \u201cBicentenario 2010\u201d, Ciudad Victoria 87087, Mexico"},{"name":"Facultad de Medicina e Ingenier\u00eda en Sistemas Computacionales de Matamoros, Universidad Aut\u00f3noma de Tamaulipas, Matamoros 87300, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5767-0676","authenticated-orcid":false,"given":"Carmen","family":"Peralta","sequence":"additional","affiliation":[{"name":"Institut d\u2019Investigacions Biom\u00e8diques August Pi I Sunyer (IDIBAPS), 08036 Barcelona, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Hep\u00e1ticas y Digestivas (CIBERehd), 08036 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2019,12,14]]},"reference":[{"key":"ref_1","first-page":"20","article-title":"Steatosis as a risk factor in liver surgery","volume":"24","author":"Gouma","year":"2007","journal-title":"Ann. 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