Basic research of the developmental mechanism and the therapeutic application of NASH by HNF4a and PPARa
Project/Area Number |
16K08728
|
Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Experimental pathology
|
Research Institution | Gunma University |
Principal Investigator |
Inoue Yusuke 群馬大学, 大学院理工学府, 准教授 (90304302)
|
Co-Investigator(Kenkyū-buntansha) |
阪口 政清 岡山大学, 医歯薬学総合研究科, 教授 (70379840)
柿崎 暁 群馬大学, 大学院医学系研究科, 講師 (80344935)
|
Project Period (FY) |
2016-04-01 – 2019-03-31
|
Project Status |
Completed (Fiscal Year 2018)
|
Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
|
Keywords | 非アルコール性脂肪性肝炎 / NASH / 脂肪酸 / 脂肪肝 / 核内受容体 / マウスモデル / HNF4α / 応用動物 / 遺伝子 |
Outline of Final Research Achievements |
We aimed to investigate the mechanism of PPARα activation in the development of NASH in HNF4α-null mice (KO mice). Expression of FATP1 was increased in KO mice, and the transactivation of FATP1 was strongly induced by PPARα. Furthermore, Decreased expression of miRNAs was identified in KO mice, and the gene involved in hepatic fibrosis was also identified as the target gene of the miRNAs. In addition, hepatic fatty acid composition was altered in KO mice with altered expression of fatty acid elongases and desaturases. These results suggests that PPARα activation by qualitative change of fatty acids might induce the development of NASH in KO mice.
|
Academic Significance and Societal Importance of the Research Achievements |
PPARα活性化はNASHを抑制すると考えられており、PPARαのアゴニストがNASHの治療薬の候補になると考えられている。本研究から、反対にPPARαの活性化がNASH発症に重要であることが分かったため、一部のNASHの治療にはPPARα阻害剤が有効であることが推測される。NASHの原因は不明な点が多く、確立された治療法もないため、より多種類の治療薬の開発が切望されていることから、本研究は従来と異なる機構による新規のNASH治療薬や診断法の開発に有意義である。
|
Report
(4 results)
Research Products
(26 results)
-
-
[Journal Article] Extracellular S100A11 plays a critical role in spread of the fibroblast population in pancreatic cancers2019
Author(s)
Takamatsu H, Yamamoto K, Tomonobu N, Murata H, Inoue Y, Yamauchi A, Sumardika W, Youyi C, Kinoshita R, Yamamura M, Fujiwara H, Mitsui Y, Araki K, Futami J, Saito K, Iioka H, Ruma MW, Putranto EW, Nishibori M, Kondo E, Yamamoto Y, Toyooka S, Sakaguchi M
-
Journal Title
Oncol Res
Volume: -
Issue: 6
Pages: 713-727
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
-
[Journal Article] Newly developed anti-S100A8/A9 monoclonal antibody efficiently prevents lung tropic cancer metastasis.2018
Author(s)
Kinoshita R, Sato H, Yamauchi A, Takahashi Y, Inoue Y, Sumardika IW, Chen Y, Tomonobu N, Araki K, Shien K, Tomida S, Torigoe H, Namba K, Kurihara E, Ogoshi Y, Murata H, Yamamoto KI, Futami J, Putranto EW, Ruma IMW, Yamamoto H, Soh J, Hibino T, Nishibori M, Kondo E, Toyooka S, Sakaguchi M.
-
Journal Title
Int J Cancer.
Volume: 印刷中
Issue: 2
Pages: 569-575
DOI
Related Report
Peer Reviewed / Int'l Joint Research
-
[Journal Article] exSSSRs (extracellular S100 soil sensor receptors)-Fc fusion proteins work as prominent decoys to S100A8/A9-induced lung tropic cancer metastasis.2018
Author(s)
Kinoshita R, Sato H, Yamauchi A, Takahashi Y, Inoue Y, Sumardika IW, Chen Y, Tomonobu N, Araki K, Shien K, Tomida S, Torigoe H, Namba K, Kurihara E, Ogoshi Y, Murata H, Yamamoto KI, Futami J, Putranto EW, Ruma IMW, Yamamoto H, Soh J, Hibino T, Nishibori M, Kondo E, Toyooka S, Sakaguchi M
-
Journal Title
Int J Cancer.
Volume: -
Issue: 12
Pages: 3138-3145
DOI
Related Report
Peer Reviewed / Int'l Joint Research
-
-
[Journal Article] Embigin Promotes Prostate Cancer Progression by S100A4-Dependent and-Independent Mechanisms.2018
Author(s)
Ruma IMW, Kinoshita R, Tomonobu N, Inoue Y, Kondo E, Yamauchi A, Sato H, Sumardika IW, Chen Y, Yamamoto KI, Murata H, Toyooka S, Nishibori M, Sakaguchi M
-
Journal Title
Cancers (Basel)
Volume: 10
Issue: 7
Pages: 239-239
DOI
Related Report
Peer Reviewed / Open Access
-
-
-
[Journal Article] An HNF4α-microRNA-194/192 signaling axis maintains hepatic cell function.2017
Author(s)
Morimoto A, Kannari M, Tsuchida Y, Sasaki S, Saito C, Matsuta T, Maeda T, Akiyama M, Nakamura T, Sakaguchi M, Nameki N, Gonzalez FJ, and Inoue Y.
-
Journal Title
J. Biol. Chem.
Volume: 292
Issue: 25
Pages: 10574-10585
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
-
[Journal Article] Expression of tumor suppressor REIC/Dkk-3 by a newly improved adenovirus vector with insertion of an hTERT promoter at the 3’-side of the transgene.2017
Author(s)
Putranto EW, Kinoshita R, Watanabe M, Sadahira T, Murata H, Yamamoto KI, Futami J, Kataoka K, Inoue Y, Ruma IM, Sumardika IW, Youyi C, Kubo M, Sakaguchi Y, Saito K, Nasu Y, Kumon H, Huh NH, and Sakaguchi M.
-
Journal Title
Oncol. Lett.
Volume: 14
Issue: 1
Pages: 1041-1048
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
-
[Journal Article] A novel partial agonist of GPBA reduces blood glucose level in a murine glucose tolerance test.2017
Author(s)
Enomoto R, Kurosawa A, Nikaido Y, Mashiko M, Saheki T, Nakajima N, Kuroiwa S, Otobe M, Ohsaki M, Tooyama K, Inoue Y, Kuwabara N, Kikuchi O, Kitamura T, Kojima I, Nakagawa Y, Saito T, Osada H, Futahashi M, Sezutsu H, and Takeda S.
-
Journal Title
Eur. J. Pharmacol.
Volume: 814
Pages: 130-137
DOI
Related Report
Peer Reviewed
-
[Journal Article] Identification of an S100A8 receptor neuroplastin-β and its heterodimer formation with EMMPRIN.2016
Author(s)
Sakaguchi M, Yamamoto M, Miyai M, Maeda T, Hiruma J, Murata H, Kinoshita R, Ruma IM, Putranto EW, Inoue Y, Morizane S, Huh NH, Tsuboi R, Hibino T.
-
Journal Title
J Invest Dermatol.
Volume: 136
Issue: 11
Pages: 2240-2250
DOI
Related Report
Peer Reviewed / Acknowledgement Compliant
-
[Journal Article] Active Secretion of Dimerized S100A11 Induced by the Peroxisome in Mesothelioma Cells.2016
Author(s)
Saho S, Satoh H, Kondo E, Inoue Y, Yamauchi A, Murata H, Kinoshita R, Yamamoto KI, Futami J, Putranto EW, Ruma IM, Sumardika IW, Youyi C, Suzawa K, Yamamoto H, Soh J, Tomida S, Sakaguchi Y, Saito K, Iioka H, Huh NH, Toyooka S, Sakaguchi M.
-
Journal Title
Cancer Microenviron.
Volume: 9
Issue: 2-3
Pages: 93-105
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
-
[Journal Article] MCAM, as a novel receptor for S100A8/A9, mediates progression of malignant melanoma through prominent activation of NF-κB and ROS formation upon ligand binding.2016
Author(s)
Ruma IM, Putranto EW, Kondo E, Murata H, Watanabe M, Huang P, Kinoshita R, Futami J, Inoue Y, Yamauchi A, Sumardika IW, Youyi C, Yamamoto K, Nasu Y, Nishibori M, Hibino T, Sakaguchi M.
-
Journal Title
Clin Exp Metastasis
Volume: 33
Issue: 6
Pages: 609-627
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
-
-
-
-
-
-
-
-
-
-
-
-