Diagnostic & Therapeutic Impact of Hepatic Non-parenchymal Cells: ADAMTS13 and the Beyonds

2016 Fiscal Year Final Research Report

• Project/Area Number: 26293287
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: General surgery
• Research Institution: Kyoto University
• Principal Investigator: Hata Koichiro 京都大学, 医学(系)研究科(研究院), 助教 (90523118)
• Co-Investigator(Kenkyū-buntansha): 上本 伸二 京都大学, 医学(系)研究科(研究院), 教授 (40252449)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: 肝移植 / 肝臓外科 / ADAMTS13 / 血栓性微小血管障害症 / 肝非実質細胞 / 星細胞 / 微小循環障害

Outline of Final Research Achievements

Hepatic IRI provoked significant reduction of ADAMTS13 activity and simultaneous vWF up-regulation. Thus, hepatic microcirculation in KO fell down to 38.4% of the pre-ischemic value, which was significantly lower than in WT (67.5%, p<0.01). Interestingly, rADAMTS13 significantly improved such microcirculatory failure up to 80.2% in KO (p<0.01), and 89.4% in WT (p<0.05). CD42b immunohistochemistry revealed massive platelet aggregation within hepatic sinusoids in KO, which was significantly attenuated by rADAMTS13 not only in KO but also in WT. Consequently, platelet counts (p<0.0001), AST (p=0.0009), ALT (p=0.0015), LDH (p=0.0011) and pro-inflammatory cytokines/chemokines (TNF-a;, IL-1b;, IL-6, IL-10, CXCL-2 and CXCL-10) were all significantly deteriorated in KO, but significantly ameliorated by rADAMTS13 administration. Notably, even in WT, rADAMTS13 significantly improved all such pathologies compared with those without.

Free Research Field

肝移植