TGF-β1 and TGF-β2 abundance in liver diseases of mice and men
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 fibr...
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| Main Authors: | , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
January 21, 2016
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| In: |
OncoTarget
Year: 2016, Volume: 7, Issue: 15, Pages: 19499-19518 |
| ISSN: | 1949-2553 |
| DOI: | 10.18632/oncotarget.6967 |
| Online Access: | Verlag, kostenfrei, Volltext: https://doi.org/10.18632/oncotarget.6967 Verlag, kostenfrei, Volltext: http://www.oncotarget.com/index.php?journal=oncotarget&page=article&op=view&path[]=6967&path[]=19757 
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| Author Notes: | Anne Dropmann, Tatjana Dediulia, Katja Breitkopf-Heinlein, Hanna Korhonen, Michel Janicot, Susanne N. Weber, Maria Thomas, Albrecht Piiper, Esther Bertran, Isabel Fabregat, Kerstin Abshagen, Jochen Hess, Peter Angel, Cédric Coulouarn, Steven Dooley, Nadja M. Meindl-Beinker |
| Summary: | 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. |
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| Item Description: | Gesehen am 02.04.2019 |
| Physical Description: | Online Resource |
| ISSN: | 1949-2553 |
| DOI: | 10.18632/oncotarget.6967 |