| First Author | Dropmann A | Year | 2016 |
| Journal | Oncotarget | Volume | 7 |
| Issue | 15 | Pages | 19499-518 |
| PubMed ID | 26799667 | Mgi Jnum | J:316576 |
| Mgi Id | MGI:6838856 | Doi | 10.18632/oncotarget.6967 |
| Citation | Dropmann A, et al. (2016) TGF-beta1 and TGF-beta2 abundance in liver diseases of mice and men. Oncotarget 7(15):19499-518 |
| abstractText | TGF-beta1 is a major player in chronic liver diseases promoting fibrogenesis and tumorigenesis through various mechanisms. The expression and function of TGF-beta2 have not been investigated thoroughly in liver disease to date. In this paper, we provide evidence that TGF-beta2 expression correlates with fibrogenesis and liver cancer development.Using quantitative realtime PCR and ELISA, we show that TGF-beta2 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-beta2 stimulation of the LX-2 cells led to upregulation of the TGF-beta receptors 1, 2, and 3, whereas TGF-beta1 treatment did not alter or decrease their expression. In liver regeneration and fibrosis upon CCl4 challenge, the transient increase of TGF-beta2 expression was accompanied by TGF-beta1 and collagen expression. In bile duct ligation-induced fibrosis, TGF-beta2 upregulation correlated with fibrotic markers and was more prominent than TGF-beta1 expression. Accordingly, MDR2-KO mice showed significant TGF-beta2 upregulation within 3 to 15 months but minor TGF-beta1 expression changes. In 5 of 8 hepatocellular carcinoma (HCC)/hepatoblastoma cell lines, relatively high TGF-beta2 expression and secretion were observed, with some cell lines even secreting more TGF-beta2 than TGF-beta1. TGF-beta2 was also upregulated in tumors of TGFalpha/cMyc and DEN-treated mice. The analysis of publically available microarray data of 13 human HCC collectives revealed considerable upregulation of TGF-beta2 as compared to normal liver.Our study demonstrates upregulation of TGF-beta2 in liver disease and suggests TGF-beta2 as a promising therapeutic target for tackling fibrosis and HCC. |
