Functional analysis of hepatic stellate cell-expressed FXR in liver cirrhosis and carcinogenesis
| Project/Area Number |
17K18012
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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 |
Pathological medical chemistry
Biological pharmacy
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| Research Institution | Osaka City University |
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Principal Investigator |
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | FXR / 肝星細胞 / 加齢 / 肝硬変 / 線維化 / 胆汁酸受容体 / 肝線維化 / 胆汁酸 / 脂肪肝炎 / 細胞老化 / 肝がん |
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| Outline of Final Research Achievements |
Bile acid receptor (Farnesoid X receptor: FXR) is an important factor for maintaining the homeostasis of bile acid, and is known to suppressively act on liver cirrhosis and liver cancer. However, FXR, which is highly expressed in hepatic stellate cells, has been suggested to have an inhibitory effect on the cultured cells, but its evaluation in vivo was poor. In the present study, mice with knockout of the FXR gene in hepatic stellate cells were observed to have increased aging-induced liver fibrosis, as in mice with a systemically deficient FXR gene. Moreover, since FXR regulates senescence-related genes in the primary human hepatic stellate cell line HHSteC, this study indicated a possibility that molecular association exists in senescence, liver fibrosis and FXR.
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| Academic Significance and Societal Importance of the Research Achievements |
肝硬変や肝がんは、背景肝疾患に関係なく、慢性肝炎の終末像であり、効果的な治療薬は存在しない。また、高齢者ほど肝硬変や肝がんが発症するリスクが高くなることが知られている。今後、加齢に伴う肝線維化亢進の分子メカニズム、細胞が老化していく過程におけるFXRの役割など、詳細な研究が必要とされるが、本研究成果は、肝星細胞のFXRを標的とする治療戦略が可能であることを示唆している。
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Report
(4 results)
Research Products
(30 results)
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[Journal Article] TGF-β-driven reduction of cytoglobin is associated with oxidative DNA damage of stellate cells in non-alcoholic steatohepatitis2020
Author(s)
Yoshinori Okina, Misako Sato-Matsubara, Tsutomu Matsubara, Atsuko Daikoku, Lisa Longato, Krista Rombouts, Le Thi Thanh Thuy, Hiroshi Ichikawa, Yukiko Minamiyama, Mitsutaka Kadota, Hideki Fujii, Masaru Enomoto, Kazuo Ikeda, Katsutoshi Yoshizato, Massimo Pinzani, Norifumi Kawada
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Journal Title
Journal of Hepatology
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Peer Reviewed / Int'l Joint Research
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[Presentation] 若年胆管癌組織を使った癌抑制遺伝子の探索2019
Author(s)
川村 悦史, 松原 勤, 樋口 萌, 出口 早苗, 高田 さゆり, 大黒 敦子, 伊藤 得路, 木下 正彦, 松原 三佐子, 小田桐 直志, 田中 肖吾, 竹村 茂一, 村上 善基, 榎本 大, 田守 昭博, 久保 正二, 祝迫 惠子, 池田 一雄, 河田 則文
Organizer
第43回日本肝臓学会西部会
Related Report
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[Presentation] TGF-β1 transcriptionally repressed cytoglobin expression and enhanced H2O2-induced oxidative DNA damage in activated HSCs.2019
Author(s)
Sato-Matsubara M, Okina Y, Matsubara T, Daikoku A, Rombouts K, Thuy LTT, Fujii H, Ikeda K, Yoshizato K, Pinzani M, Kawada N.
Organizer
20th International Symposium on Cells of Hepatic Sinusoid
Related Report
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[Presentation] TGFβ1 reduces Cytoglobin expression via Smad2-SP3 pathway in human, but not mouse, hepatic stellate cells2018
Author(s)
Sato-Matsubara M, Okina Y, Matsubara T, Daikoku A, Fujii H, Rombouts K, Ikeda K, Yoshizato K, Pinzani M, Kawada N.
Organizer
AASLD single topic conference; Hepatic fibrosis
Related Report
Int'l Joint Research
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