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 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 (渡邉 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
|
Project Status |
Completed (Fiscal Year 2017)
|
Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
|
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.
|