Protective role of CYGB in prevention of liver fibrosis development in vitro and in vivo
Project/Area Number |
16K19363
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Research Category |
Grant-in-Aid for Young Scientists (B)
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Allocation Type | Multi-year Fund |
Research Field |
Gastroenterology
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Research Institution | Osaka City University |
Principal Investigator |
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Project Period (FY) |
2016-04-01 – 2019-03-31
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Project Status |
Completed (Fiscal Year 2018)
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Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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Keywords | Cytoglobin / Hepatic stellate cells / Liver Fibrosis / cytoglobin / Hepatic Stellate Cells / Liver fibrosis / HCC / liver fibrosis / hepatic stellate cells / fibrosis / cholestasis / ウイルス / 肝臓学 |
Outline of Final Research Achievements |
Cygb deficient mice, Cygb overexpressing mice, and recombinant human CYGB protein were generated in our laboratory. The role of Cygb in anti-fibrosis and cancer were examined in different models of liver injuries including (1) chemical induced liver fibrosis using thioacetamide (TAA) treatment for 10 weeks; (2) diet induced non-alcoholic fatty liver diseases (NASH) using choline deficient amino acid define (CDAA) diet for 16 weeks. We found that in the absence of Cygb liver injuries were magnified in Cygb-KO mice. In contrast, Cygb overexpression protected mice from liver damage induced by different etiologies. Furthermore, we produced rhCYGB protein and found that rhCYGB possess antioxidant and peroxidase activities. In vivo model, rhCYGB administration in TAA-treated mice inhibited liver injuries, inflammation and fibrosis development. Thus, CYGB with ROS scavenger could play an important role for preventing from liver fibrosis.
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Academic Significance and Societal Importance of the Research Achievements |
Cygbの機能の継続的な解明、特に肝臓、最大の外分泌腺および内分泌腺の障害へのその寄与、ならびに線維症および腫瘍形成の予防におけるその役割は、極めて重要である。 HSCにおけるCygbの存在とその影響を理解することは、そのプロテアチンの特徴に関連した多くの展開する謎を持つ特別な細胞であり、依然として挑戦的です。さらに、HSCに対するCygb依存性の効果は、肝細胞の機能および表現型に間接的に影響を及ぼし得ると推測される。我々のCygb欠損マウスおよびCygb-過剰発現マウスは、線維症発生中のHSCにおけるCYGBの関与を研究し、その作用機序を探究するためのユニークで価値のあるモデルであろう。
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Report
(4 results)
Research Products
(25 results)
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[Journal Article] The Hemoglobin Homolog Cytoglobin in Smooth Muscle Inhibits Apoptosis and Regulates Vascular Remodeling2017
Author(s)
3.Jourd'heuil FL, Xu H, Reilly T, McKellar K, El Alaoui C, Steppich J, Liu YF, Zhao W, Ginnan R, Conti D, Lopez-Soler R, Asif A, Keller RK, Schwarz JJ, Thanh Thuy LT, Kawada N, Long X, Singer HA, Jourd'heuil D.
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Journal Title
Arterioscler Thromb Vasc Biol.
Volume: 37(10)
Issue: 10
Pages: 1944-1955
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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[Journal Article] Cytoglobin Regulates Blood Pressure and Vascular Tone through Nitric Oxide Metabolism in the Vascular Wall.2017
Author(s)
4.Xiaoping Liu, Mohamed A. El-Mahdy, James Boslett, Saradhadevi Varadharaj, Craig, Hemann, Tamer M. Abdelghany, Raed S. Ismail, Sean C. Little, Danlei Zhou, Le Thi Thanh Thuy, Norifumi Kawada, and Jay L. Zweier.
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Journal Title
Nature Communications.
Volume: 8
Issue: 1
Pages: 14807-14807
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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