| Budget Amount *help |
¥23,660,000 (Direct Cost: ¥18,200,000、Indirect Cost: ¥5,460,000)
Fiscal Year 2015: ¥7,150,000 (Direct Cost: ¥5,500,000、Indirect Cost: ¥1,650,000)
Fiscal Year 2014: ¥7,150,000 (Direct Cost: ¥5,500,000、Indirect Cost: ¥1,650,000)
Fiscal Year 2013: ¥9,360,000 (Direct Cost: ¥7,200,000、Indirect Cost: ¥2,160,000)
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| Outline of Final Research Achievements |
Our previous studies demonstrated that hepatocytes could be converted into biliary lineage cells through activation of Notch signaling in liver diseases. In this study, we found that, in a mouse model of intrahepatic cholangiocarcinoma, hepatic macrophages called Kupffer cells express the Notch ligand Jagged-1 coincident with Notch activation in pericentral hepatocytes, and depletion of Kupffer cells prevents the Notch-mediated cell-fate conversion of hepatocytes to biliary lineage cells. Meanwhile, we also found that hepatic progenitor cells (HPCs), which arise from hepatocytes in a chronically injured liver, can give rise to myofibroblasts, in addition to hepatocytes and cholangiocytes, as descendants. During tumor development, HPCs can contribute to the formation of the tumor microenvironment by producing abundant myofibroblasts. These findings will be useful for uncovering the pathogenic mechanism of liver diseases and developing therapeutic strategies for such diseases.
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