Research on molecular mechanisms underlying terminal differentiation of hepatic stem/progenitor cells via non-canonical Wnt signaling pathways

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K08989
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: AZUMA Seishin (陳正新) 東京医科歯科大学, 医学部附属病院, 講師 (10376783)
• Co-Investigator(Kenkyū-buntansha): 柿沼 晴 東京医科歯科大学, 大学院医歯学総合研究科, 寄附講座准教授 (30372444) ; 朝比奈 靖浩 東京医科歯科大学, 大学院医歯学総合研究科, 寄附講座教授 (00422692) ; 渡辺 守 東京医科歯科大学, 大学院医歯学総合研究科, 教授 (10175127)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: 幹細胞 / 発生・分化 / 再生医学 / 肝疾患治療 / シグナル調節

Outline of Final Research Achievements

This research project has investigated on the molecular mechanisms underlying terminal differentiation of hepatic stem/progenitor cells via non-canonical Wnt signaling pathways.
Screening using transcriptome analysis revealed that Wnt5a signaling is associated with Bone morphogenetic protein-4 (BMP-4) signaling pathway in hepatic stem/progenitor cells. BMP-4-mediated signaling suppressed the proliferation and biliary luminal formation of hepatic stem/progenitor cells. BMP-4 signaling promoted the hepatic maturation of hepatic stem/progenitor cells. Moreover, Wnt5a and BMP-4 coordinately suppressed proliferation and cholangiocytic luminal formation of hepatic stem/progenitor cells. Our data also showed that Matrix Metalloproteinase-14-mediated signaling accelerated the biliary luminal formation of hepatic stem/progenitor cells.
These studies can contribute to the progress of regenerative medical science in the field of liver diseases.

Free Research Field

消化器病学