Diagnostic & Therapeutic Impact of Hepatic Non-parenchymal Cells: ADAMTS13 and the Beyonds
| Project/Area Number |
26293287
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Partial Multi-year Fund |
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| Section | 一般 |
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| Research Field |
General surgery
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| Research Institution | Kyoto University |
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Principal Investigator |
Hata Koichiro 京都大学, 医学(系)研究科(研究院), 助教 (90523118)
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| Co-Investigator(Kenkyū-buntansha) |
上本 伸二 京都大学, 医学(系)研究科(研究院), 教授 (40252449)
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| Project Period (FY) |
2014-04-01 – 2017-03-31
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| Project Status |
Completed (Fiscal Year 2016)
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| Budget Amount *help |
¥16,120,000 (Direct Cost: ¥12,400,000、Indirect Cost: ¥3,720,000)
Fiscal Year 2016: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
Fiscal Year 2015: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2014: ¥7,540,000 (Direct Cost: ¥5,800,000、Indirect Cost: ¥1,740,000)
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| 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 / 肝虚血再灌流障害 / 血小板血栓 / 過小グラフト症候群 / 生体部分肝移植 / TMA / 虚血再灌流 / 血栓性微小血管障害 |
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| 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.
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Report
(5 results)
Research Products
(37 results)
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[Journal Article] Impact of Donor Age on Recipient Survival in Adult-to-adult Living-donor Liver Transplantation.2017
Author(s)
Kubota T, Hata K, Sozu T, Ueda Y, Hirao H, Okamura Y, Tamaki I, Yoshikawa J, Kusakabe J, Uemoto S, et al.
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Journal Title
Annals of Surgery
Volume: In Press
Issue: 6
Pages: 1126-1133
DOI
Related Report
Peer Reviewed
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[Journal Article] Portal vein reconstruction using vein grafts in pediatric living donor liver transplantation: Current status.2017
Author(s)
Sabra TA, Okajima H, Yoshizawa A, Okamoto T, Anazawa T, Ygi S, Hata K, Yasuchika K, Taura K, Hatano E, Kaido T, Uemoto S.
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Journal Title
Pediatric Transplantation
Volume: In Press
Issue: 3
DOI
Related Report
Peer Reviewed
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[Journal Article] Impact of Subnormothermic Machine Perfusion Preservation in Severely Steatotic Rat Livers: A Detailed Assessment in an Isolated Setting.2017
Author(s)
Okamura Y, Hata K, Tanaka H, Hirao H, Kubota T, Inamoto O, Kageyama S, Tamaki I, Yermek N, Yoshikawa J, Uemoto S.
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Journal Title
American Journal of Transplantation
Volume: In Press
Issue: 5
Pages: 1204-1215
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Influence of hepatorenal syndrome on outcome of living donor liver transplantation: A single-center experience in 357 patients.2017
Author(s)
Okamura Y, Hata K, Inamoto O, Kubota T, Hirao H, Tanaka H, Fujimoto Y, Ogawa K, Mori A, Okajima H, Kaido T, Uemoto S.
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Journal Title
Hepatology Research
Volume: 47
Issue: 5
Pages: 425-434
DOI
Related Report
Peer Reviewed
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[Presentation] IMPACT OF ADAMTS13, VON WILLEBRAND FACTOR-CLEAVING PROTEASE, ON HEPATIC ISCHEMIA/REPERFUSION INJURY2015
Author(s)
Hirofumi Hirao, Koichiro Hata, Hirokazu Tanaka, Shoichi Kageyama, Yusuke Okamura, Toyonari Kubota, Osamu Inamoto, Kentaro Kadono, and Shinji Uemoto
Organizer
17th Congress of the European Society for Organ Transplantation
Place of Presentation
ブリュッセル、ベルギー
Year and Date
2015-09-13
Related Report
Int'l Joint Research
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[Presentation] Post-operative thrombocytopenia may determine the fate of adult-to-adult living donor partial liver transplantation; Proposal of “Thrombotic Microangiopathy (LTx-TMA) Score”.2015
Author(s)
Hirokazu Tanaka, Koichiro Hata, Hirofumi Hirao, Yusuke Okamura, Toyonari Kubota, Osamu Inamoto, Shoichi Kageyama, Kohei Ogawa, Yasuhiro Fujimoto, Akira Mori, Hideaki Okajima, Toshimi Kaido, and Shinji Uemoto
Organizer
17th Congress of the European Society for Organ Transplantation
Place of Presentation
ブリュッセル、ﾍﾞﾙｷﾞｰ
Year and Date
2015-09-13
Related Report
Int'l Joint Research
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[Presentation] Impact of Donor Age on the Outcome of Adult Living Donor Partial Liver Transplantation: Single-Center Experience in 316 Patients2015
Author(s)
Toyonari Kubota1, Koichiro Hata1, Takashi Sozu2, Hirokazu Tanaka1, Hirofumi Hirao1, Yusuke Okamura1, Osamu Inamoto1, Kohei Ogawa1, Yasuhiro Fujimoto1, Akira Mori1, Hideaki Okajima1, Toshimi Kaido1, and Shinji Uemoto1
Organizer
17th Congress of the European Society for Organ Transplantation
Place of Presentation
ブリュッセル、ﾍﾞﾙｷﾞｰ
Year and Date
2015-09-13
Related Report
Int'l Joint Research
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