Functional analysis of hepatic mesothelium-derived angiogenic factors in embryonic hepatic histogenesis

2014 Fiscal Year Final Research Report

• Project/Area Number: 22390034
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: General anatomy (including Histology/Embryology)
• Research Institution: Fukushima Medical University (2014); Kumamoto University (2010-2013)
• Principal Investigator: YOKOUCHI Yuji 福島県立医科大学, 医学部, 教授 (60252227)
• Co-Investigator(Kenkyū-buntansha): YAMAMURA Ken-ichi 熊本大学, 生命資源研究・支援センター, シニア教授 (90115197)
• Co-Investigator(Renkei-kenkyūsha): YAMAMURA Ken-ichi 熊本大学, 生命資源研究・支援センター, シニア教授 (90115197)
• Project Period (FY): 2010-04-01 – 2015-03-31
• Keywords: 細胞組織 / 発生分化 / 肝臓 / 再生医学 / TGF-beta / WT1 / Tek / FoxA2

Outline of Final Research Achievements

The embryonic liver tissue is autonomously formed by the intracellular interactions among hepatoblasts and other mesenchymal cells. However, the understanding is not sufficient for application in regenerative medicine. In the embryonic mouse liver, TGF-betas are expressed in hepatoblasts and in hepatic mesothelial layer. But, the roles in each cell-lineage have not be analyzed yet. Here, to perform the functional analysis of TGF-beta signaling pathway in hepatoblasts and hepatic mesothelial cell-lineage during the hepatic histogenesis, we conditionally expressed the dominant negative form of human ALK5 in each cell-lineage. In hepatoblasts, forced expression of dnALK5 caused dysgenesis of hepatic epithelia. In hepatic mesothelial cell-lineaege, the forced expression caused dysgenesis of hepatic mesothelium and derivatives. These data indicate that the TGF-beta pathway is involved in branching of hepatoblast cords and maintenance and differentiation of hepatic mesothelial cell-lineage.

Free Research Field

発生生物学