Transgenic expression of tgfb1a induces hepatic inflammation, fibrosis and metastasis in zebrafish.

TGFB signaling pathway plays a key role on liver disease progression. In our previous study, we have demonstrated the oncogenic ability of Tgfb signaling pathway as a chronic induction of tgfb1a specifically in hepatocytes led to both hepatocellular carcinoma (HCC) and cholangiocarcinoma in zebrafish. Here we would like to examine the potential mechanisms of Tgfb1a induced tumorigenesis. As majority of HCC developed from the background of liver inflammation and fibrosis, by immune-fluorescent staining on markers of liver inflammation, we indeed observed a progressively increased liver inflammation during tumorigenesis. Examination of liver fibrosis also revealed marked increase of liver fibrosis during early liver tumorigenesis and it was dramatically dropped in late liver tumorigenesis. Hence, induction of tgfb1a drives HCC through association of liver inflammation and fibrosis. Furthermore, we found high expression of EMT markers in late liver tumorigenesis, indicating a tumor metastasis potential. These observations are generally consistent with the molecular mechanisms of hepatocarcinogenesis in human.