The Effect of Fibroblast Growth Factor 15 Signaling in Non-Steatotic and Steatotic Liver Transplantation from Cardiocirculatory Death

Autor:	José Gulfo, María Eugenia Cornide-Petronio, Araní Casillas-Ramírez, Cindy G Avalos-de León, Carmen A. Peralta, Floriana Rotondo, Mónica B. Jiménez-Castro, Jordi Gracia-Sancho
Jazyk:	angličtina
Rok vydání:	2019
Předmět:	Male 0301 basic medicine steatotic liver grafts medicine.medical_treatment Endogeny FGF15 Protein Serine-Threonine Kinases Liver transplantation Fibroblast growth factor Cholesterol 7 alpha-hydroxylase Article ischemia-reperfusion damage Bile Acids and Salts 03 medical and health sciences 0302 clinical medicine CYP27A1 medicine Animals Cholesterol 7-alpha-Hydroxylase Cell Proliferation Heart Failure cardiocirculatory death liver transplantation Chemistry YAP-Signaling Proteins General Medicine medicine.disease Rats Rats Zucker Fatty Liver Fibroblast Growth Factors Transplantation 030104 developmental biology Liver Reperfusion Injury Cancer research 030211 gastroenterology & hepatology Steatosis Apoptosis Regulatory Proteins Signal Transduction
Zdroj:	Cells Volume 8 Issue 12
ISSN:	2073-4409
DOI:	10.3390/cells8121640
Popis:	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.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::c567e5f8880768be723c54c91db04465 Zobrazit plný text záznamu Plný text ve formátu PDF Plný text ve formátu HTML
Nepřihlášeným uživatelům se plný text nezobrazuje	K zobrazení výsledku je třeba se přihlásit.