Utilization of RCAS-TVA system to study FGF10/FGFR2b in fetal hepatocyte proliferation, maturation and liver regeneration

• Main Authors: Heui-wen Wang, 王慧雯
• Other Authors: 王文柄
• Format: Others
• Language: zh-TW
• Online Access: http://ndltd.ncl.edu.tw/handle/qt9kr8

碩士 === 慈濟大學 === 分子生物及細胞生物研究所 === 96 === Liver development and regeneration share the requirement for concurrent proliferation and obtaining of highly specialized cellular functions. Many signaling pathways are involved to regulate both processes. It has been reported that FGF10 can promote the survival of hepatoblasts during liver development. In adult mouse liver, inhibition of FGFR2 signaling results in delayed regeneration after PH. However, the importance of FGF10/FGFR2b signaling pathway in proliferation/differentiation of fetal hepatocytes or liver regeneration in adult mice is still unclear. To study the effects of FGF10/FGFR2b in these two processes, RCAS-TVA system was used in this study. A TVA receptor was expressed in the hepatocytes of Albumin-TVA transgenic mice thus allowed specific infection of RCAS retroviruses carrying genes. Marker viruses including RCAS-AP, RCAS-eGFP and RCAS-luciferase exhibited efficient infection in both adult and fetal hepatocytes. More PCNA (+), BrdU (+) and H3P (+) hepatocytes were observed after infection of RCAS-FGF10 in the regenerating liver after partial hepatectomy (PH). In addition, we also inhibited the FGF signaling with RCAS virus carrying soluble dominant negative FGFR2b, dn-FGFR2b. The result showed a decreased number of BrdU(＋) hepatocytes in dn-FGFR2b-expressing liver after PH. We also tried to evaluate the role of FGF10/FGFR2b signaling in the differentiation and proliferation of fetal hepatocytes. However, we have not obtained clear results yet. To sum up, we found that FGF10/FGFR2b pathway might regulate proliferation and promote cell cycle progression during liver regeneration.