Development of anti-fibrotic therapies for liver fibrosis by the regulation of Rho family GTPases of macrophages.
| Project/Area Number |
16K21193
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Medical pharmacy
Gastroenterology
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| Research Institution | Yamaguchi University |
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Principal Investigator |
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| Research Collaborator |
NISHI Maiko
MATSUURA Keiji
FUJISAWA Koich
TAKAMI Taro
YAMAMOTO Naoki
SUEHIRO Yutaka
YAMASAKI Takahiro
SAKAIDA Isao
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| Project Period (FY) |
2016-04-01 – 2018-03-31
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| Project Status |
Completed (Fiscal Year 2017)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2017: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2016: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | 肝線維化 / Rho family GTPase / マクロファージ / 肝硬変 / R-Ketorolac / 線維溶解 / アクチン重合 |
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| Outline of Final Research Achievements |
Liver fibrosis is regulated by interaction between macrophage (Mφ) and hepatic stellate cell (HSC). We hypothesized that alterations in cell shape via actin remodeling may modulate the phenotype of Mφ and HSC in fibrotic liver. We therefore examined the effects of Rho family GTPase inhibitors, which regulate actin remodeling, on MMPs expression of Mφ and activation of HSC, with the aim of developing future anti-fibrotic therapies.
Treatment with the Rac1/Cdc42 inhibitor, R-Ketorolac, inhibited actin remodeling, while it had no impact on MMPs expression of murine Mφ in vitro and in vivo. The Rac1 inhibitor, NSC23766-treated mice showed a higher number of MMP9 positive cells in the liver and reduced liver fibrosis. Transfection of miR142-3p, which targets Rho family GTPase genes including Rac1, increased MMP12 expression in human Mφ, while it increased MMP1 and BAMBI expression in human HSC.
These results suggest that Rho family GTPases may be a target for anti-fibrotic therapy.
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Report
(3 results)
Research Products
(16 results)
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[Journal Article] A canine liver fibrosis model to develop a therapy for liver cirrhosis using cultured bone marrow-derived cells.2017
Author(s)
Matsuda T, Takami T, Sasaki R, Nishimura T, Aibe Y, Paredes BD, Quintanilha LF, Matsumoto T, Ishikawa T, Yamamoto N, Tani K, Terai S, Taura Y, Sakaida I.
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Journal Title
Hepatology Communications
Volume: 1
Issue: 7
Pages: 691-703
DOI
Related Report
Peer Reviewed / Open Access
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[Presentation] Nonclinical proof-of-concept for "hepatic artery infusion of cultured autologous bone marrow mesenchymal stem cells" in a canine liver fibrosis model2017
Author(s)
Tatsuro Nishimura, Taro Takami, Ryo Sasaki, Yuki Aibe, Takashi Matsuda, Toshihiko, Matsumoto, Koichi Fujisawa, Naoki Yamamoto, Isao Sakaida
Organizer
The Liver Meeting 2017, AASLD
Related Report
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