The role of blood coagulation and fibrinolysis system in the oxaliplatin-induced liver sinusoidal obstruction syndrome
| Project/Area Number |
16H07357
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| Research Category |
Grant-in-Aid for Research Activity Start-up
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| Allocation Type | Single-year Grants |
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| Research Field |
Digestive surgery
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| Research Institution | Kindai University |
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Principal Investigator |
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| Research Collaborator |
KAJI Hiroshi 近畿大学, 医学部, 教授 (90346255)
Mackman Nigel University of North Carolina at Chapel Hill, Professor
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| Project Period (FY) |
2016-08-26 – 2018-03-31
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| Project Status |
Completed (Fiscal Year 2017)
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| Budget Amount *help |
¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | 肝類洞閉塞症候群 / 凝固因子 / 線溶因子 / PAI-1 / 組織因子 / TF / オキサリプラチン / 組織因子 (TF) / ADAMTS13 / 凝固 / 線溶 / tissue factor |
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| Outline of Final Research Achievements |
The objective of this study was to clarify the role of coagulation and fibrinolysis system, especially plasminogen activator inihibitor-1 (PAI-1) and tissue factor (TF), in the diathesis of oxaliplatin-induced liver sinusoidal obstruction syndrome (SOS).
Repeated administration of oxaliplatin to the wild-type mice significantly increased PAI-1 mRNA levels in the liver, whereas TF mRNA levels were decreased. The increase rate of liver PAI-1 mRNA was significantly and negatively correlated with the rate of body weight loss of the mice.The increases of inflammatory cytokines and fibrosis markers in the liver of PAI-1 deficient mice were milder than WT mice. TF-deficient mice showed higher mortality and severe body weight loss compared with WT mice.
Therefore, in the SOS pathogenesis, PAI-1 may play an important role in accelerating liver injury by forming multiple microthrombi in the liver microcirculation, resulting in enhanced inflammation and fibrosis.
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Report
(3 results)
Research Products
(17 results)
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[Journal Article] Adult hepatocytes direct liver organogenesis through non-parenchymal cell recruitment in the kidney.2018
Author(s)
Utoh R, Komori J, Kuge H, Tatsumi K, Yamada M, Hirohashi S, Tsutsumi M, Amanuma T, Yoshioka A, Nakajima Y, Wake K, Okano T, Lagasse E, Ohashi K.
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Journal Title
J Hepatol.
Volume: 68
Issue: 4
Pages: 744-753
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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