Please use this identifier to cite or link to this item:
http://hdl.handle.net/2445/97581
Title: | TGF-β1 and TGF-β2 abundance in liver diseases of mice and men |
Author: | Dropmann, Anne Dediulia, Tatjana Breitkopf-Heinlein, Katja Korhonen, Hanna Janicot, Michel Weber, Susanne N. Thomas, Maria Piiper, Albrecht Bertran Rodríguez, Esther Fabregat Romero, Isabel Abshagen, Kerstin Hess, Jochen Angel, Peter Coulouarn, Cédric Dooley, Steven Meindl-Beinker, Nadja M. |
Keywords: | Malalties del fetge Fibrosi quística Ratolins (Animals de laboratori) Regeneració (Biologia) Liver diseases Cystic fibrosis Mice (Laboratory animals) Regeneration (Biology) |
Issue Date: | 21-Jan-2016 |
Publisher: | Impact Journals |
Abstract: | TGF-β1 is a major player in chronic liver diseases promoting fibrogenesis and tumorigenesis through various mechanisms. The expression and function of TGF-β2 have not been investigated thoroughly in liver disease to date. In this paper, we provide evidence that TGF-β2 expression correlates with fibrogenesis and liver cancer development. Using quantitative realtime PCR and ELISA, we show that TGF-β2 mRNA expression and secretion increased in murine HSCs and hepatocytes over time in culture and were found in the human-derived HSC cell line LX-2. TGF-β2 stimulation of the LX-2 cells led to upregulation of the TGF-β receptors 1, 2, and 3, whereas TGF-β1 treatment did not alter or decrease their expression. In liver regeneration and fibrosis upon CCl4 challenge, the transient increase of TGF-β2 expression was accompanied by TGF-β1 and collagen expression. In bile duct ligation-induced fibrosis, TGF-β2 upregulation correlated with fibrotic markers and was more prominent than TGF-β1 expression. Accordingly, MDR2-KO mice showed significant TGF-β2 upregulation within 3 to 15 months but minor TGF-β1 expression changes. In 5 of 8 hepatocellular carcinoma (HCC)/hepatoblastoma cell lines, relatively high TGF-β2 expression and secretion were observed, with some cell lines even secreting more TGF-β2 than TGF-β1. TGF-β2 was also upregulated in tumors of TGFα/cMyc and DEN-treated mice. The analysis of publically available microarray data of 13 human HCC collectives revealed considerable upregulation of TGF-β2 as compared to normal liver. Our study demonstrates upregulation of TGF-β2 in liver disease and suggests TGF-β2 as a promising therapeutic target for tackling fibrosis and HCC. |
Note: | Reproducció del document publicat a: http://dx.doi.org/10.18632/oncotarget.6967 |
It is part of: | Oncotarget, 2016, vol. 7, num. 15, p. 19499-19518 |
URI: | http://hdl.handle.net/2445/97581 |
Related resource: | http://dx.doi.org/10.18632/oncotarget.6967 |
ISSN: | 1949-2553 |
Appears in Collections: | Articles publicats en revistes (Ciències Fisiològiques) Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL)) |
Files in This Item:
File | Description | Size | Format | |
---|---|---|---|---|
657826.pdf | 2.65 MB | Adobe PDF | View/Open |
This item is licensed under a Creative Commons License