1. Главная
  2. Ресурсы
  3. Библиотечный поиск
Ileal FGF15contributes tofibrosis‐associatedhepatocellularcarcinoma development Iker UriarteMaría U. LatasaSimone Carotti2014 год

Ileal FGF15 contributes to fibrosis‐associated hepatocellular carcinoma development
статья из журнала

Страница публикацииПубликация в OpenAlex
Аннотация: 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.
Год издания: 2014
Авторы: Iker Uriarte, María U. Latasa, Simone Carotti, Maite G. Fernández‐Barrena, Oihane García‐Irigoyen, María Elizalde, Raquel Urtasun, Umberto Vespasiani‐Gentilucci, S. Morini, Álvaro de Mingo Pulido, Montserrat Marı́, Fernando J. Corrales, Jesús Prìeto, Carmen Berasain, Matías A. Ávila
Издательство: Wiley
Источник: International Journal of Cancer
Ключевые слова: Fibroblast Growth Factor Research, Kruppel-like factors research, Epigenetics and DNA Methylation
Другие ссылки: International Journal of Cancer (HTML)
PubMed (HTML)