Por favor, use este identificador para citar o enlazar a este item:
http://hdl.handle.net/10261/124609COMPARTIR / EXPORTAR:
 SHARE
 CORE
BASE
|
|
| Visualizar otros formatos: MARC | Dublin Core | RDF | ORE | MODS | METS | DIDL | DATACITE | |
| Título: | Ileal FGF15 contributes to fibrosis-associated hepatocellular carcinoma development |
Autor: | Uriarte, Iker; Mingo, Álvaro de CSIC; Marí, Montserrat CSIC ORCID ; Ávila, Matías A. CSIC ORCID | Palabras clave: | connective tissue growth factor fibroblast growth factor 15/19 fibrosis |
Fecha de publicación: | 6-nov-2014 | Editor: | John Wiley & Sons International Union against Cancer |
Citación: | International Journal of Cancer 136(19): 2469-2475 (2015) | Resumen: | © 2014 UICC. Fibroblast growth factor 15 (FGF15), FGF19 in humans, is a gut-derived hormone and a key regulator of bile acids and carbohydrate metabolism. FGF15 also participates in liver regeneration after partial hepatectomy inducing hepatocellular proliferation. FGF19 is overexpressed in a significant proportion of human hepatocellular carcinomas (HCC), and activation of its receptor FGFR4 promotes HCC cell growth. Here we addressed for the first time the role of endogenous Fgf15 in hepatocarcinogenesis. Fgf15+/ + and Fgf15-/- mice were subjected to a clinically relevant model of liver inflammation and fibrosis-associated carcinogenesis. Fgf15-/- mice showed less and smaller tumors, and histological neoplastic lesions were also smaller than in Fgf15+/ + animals. Importantly, ileal Fgf15 mRNA expression was enhanced in mice undergoing carcinogenesis, but at variance with human HCC it was not detected in liver or HCC tissues, while circulating FGF15 protein was clearly upregulated. Hepatocellular proliferation was also reduced in Fgf15-/- mice, which also expressed lower levels of the HCC marker alpha-fetoprotein (AFP). Interestingly, lack of FGF15 resulted in attenuated fibrogenesis. However, in vitro experiments showed that liver fibrogenic stellate cells were not direct targets for FGF15/FGF19. Conversely we demonstrate that FGF15/FGF19 induces the expression of the pro-fibrogenic and pro-tumorigenic connective tissue growth factor (CTGF) in hepatocytes. These findings suggest the existence of an FGF15-triggered CTGF-mediated paracrine action on stellate cells, and an amplification mechanism for the hepatocarcinogenic effects of FGF15 via CTGF production. In summary, our observations indicate that ileal FGF15 may contribute to HCC development in a context of chronic liver injury and fibrosis. | Descripción: | Iker Uriarte et al. | Versión del editor: | http://dx.doi.org/10.1002/ijc.29287 | URI: | http://hdl.handle.net/10261/124609 | DOI: | 10.1002/ijc.29287 | Identificadores: | doi: 10.1002/ijc.29287 issn: 1097-0215 |
| Aparece en las colecciones: | (IIBB) Artículos |
Ficheros en este ítem:
| Fichero | Descripción | Tamaño | Formato | |
|---|---|---|---|---|
| accesoRestringido.pdf | 15,38 kB | Adobe PDF |  Visualizar/Abrir |
CORE Recommender
SCOPUSTM
Citations
74
checked on 10-abr-2024
WEB OF SCIENCETM
Citations
74
checked on 28-feb-2024
Page view(s)
271
checked on 18-abr-2024
Download(s)
132
checked on 18-abr-2024
Google ScholarTM
Check
Altmetric
Altmetric
NOTA: Los ítems de Digital.CSIC están protegidos por copyright, con todos los derechos reservados, a menos que se indique lo contrario.