The study for the protective response by innate immune system and functional specialization of Kupffer cells in the pathogenesis of NASH
Project/Area Number |
26461010
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Gastroenterology
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Research Institution | Kochi University |
Principal Investigator |
ONO Masafumi 高知大学, 教育研究部医療学系臨床医学部門, 准教授 (70304681)
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Co-Investigator(Kenkyū-buntansha) |
中島 弘幸 防衛医科大学校(医学教育部医学科進学課程及び専門課程、動物実験施設、共同利用研究, 免疫・微生物学, 助教 (10574064)
西原 利治 高知大学, 教育研究部医療学系臨床医学部門, 教授 (60145125)
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Project Period (FY) |
2014-04-01 – 2017-03-31
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Project Status |
Completed (Fiscal Year 2016)
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Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2016: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2014: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
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Keywords | NASH / Kupffer細胞 / CD68+Kupffer細胞 / CD11b+Kupffer細胞 / 腸内細菌 / NASH / 肝臓学 / CD11b+Kupffer細胞 |
Outline of Final Research Achievements |
Although impairment of Kupffer cells are important for the pathogenesis of nonalcoholic steatohepatitis (NASH), the precise mechanisms of the impairment have not been well clarified yet. In this study, we have clarified that the CD11b+Kupffer cells increased and CD68+Kupffer cells decreased in the liver of NASH. In addition, inflammation and fibrosis were improved without attenuation of hepatic steatosis, when CD11b+Kupffer cells were decreased by exposing of 1Gy irradiation. In contrast, depletion of the resident subset, CD68+Kupffer cells, by clodronate liposome (c-lipo) treatment exacerbated disease progression. It was clarified that recruited CD11b+ CD68+ Kupffer cells may play an essential role in steatohepatitis and fibrosis in the pathogenesis of NASH. We concluded that recruitment and activation of bone marrow derived macrophages, CD11b+Kupffer cells, may have the important key factor to develop steatohepatitis from simple steatosis.
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Report
(4 results)
Research Products
(89 results)
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[Journal Article] Hepatocellular carcinoma in Japanese patients with nonalcoholic fatty liver disease and alcoholic liver disease: multicenter survey.2016
Author(s)
Tokushige K, Hyogo H, Nakajima T, Ono M, Kawaguchi T, Honda K, Eguchi Y, Nozaki Y, Kawanaka M, Tanaka S, Imajo K, Sumida Y, Kamada Y, Fujii H, Suzuki Y, Kogiso T, Karino Y, Munekage K, Kuromatsu R, Oeda S, Yanase M, Mori K, Ogawa Y, Seko Y, Takehara T, Itoh Y, Nakajima A, Kanemasa K, Saibara T
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Journal Title
J Gastroenterol
Volume: 印刷中
Issue: 6
Pages: 586-96
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Magnetic Resonance Imaging More Accurately Classifies Steatosis and Fibrosis in Nonalcoholic Fatty Liver Disease Than Transient Elastography.2016
Author(s)
Imajo K, Kessoku T, Honda Y, Tomeno W, Ogawa Y, Mawatari H, Fujita K, Yoneda M, Taguri M, Hyogo H, Sumida Y, Ono M, Eguchi Y, Inoue T,Yamanaka T, Wada K, Saito S, Nakajima A
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Journal Title
Gastroenterology
Volume: 150
Issue: 3
Pages: 626-37
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Suppression of miR-7 biogenesis by NF90-NF45 controls cell proliferation in hepatocellular carcinoma.2016
Author(s)
Higuchi T, Todaka H, Sugiyama Y, Ono M, Tamaki N, Hatano E, Takezaki Y, Hanazaki K, Miwa T, Chin See LS, Morisawa K, Tsuda M, Taniguchi T, Sakamoto S
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Journal Title
J Biol Chem
Volume: 291
Pages: 21074-21084
Related Report
Peer Reviewed
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[Journal Article] PNPLA3 is involved in hepatic fatty acid and triglyceride metabolism through XBP1 and modulation of endoplasmic reticulum stress in mice.2016
Author(s)
Ochi T, Munekage K, Ono M, Higuchi T, Tsuda M, Hayashi Y, Okamoto N, Toda K, Sakamoto S, Oben JA, Saibara T
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Journal Title
Hepatol Res
Volume: 印刷中
Issue: 6
Pages: 584-592
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] A successful case of deceased donor liver transplantation for a patient with intrahepatic arterioportal fistula.2015
Author(s)
Takagi K, Yagi T, Yoshida R, Shinoura S, Umeda Y, Nobuoka D, Watanabe N, Kuise T, Sui K, Hirose A, Tsuboi M, Ogasawara M, Iwasaki S, Saibara T, Fujiwara T.
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Journal Title
Hepatol Res.
Volume: -
Issue: 13
Pages: 1409-1415
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] A novel noninvasive diagnostic method for nonalcoholic steatohepatitis using two glycobiomarkers.2015
Author(s)
Kamada Y, Ono M, Hyogo H, Fujii H, Sumida Y, Mori K, Tanaka S, Yamada M, Akita M, Mizutani K, Fujii H, Yamamoto A, Takamatsu S, Yoshida Y, Itoh Y, Kawada N, Chayama K, Saibara T, Takehara T, Miyoshi E
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Journal Title
Hepatology.
Volume: 62
Issue: 5
Pages: 1433-1443
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] Evidence-based clinical practice guidelines for nonalcoholic fatty liver disease/nonalcoholic steatohepatitis.2015
Author(s)
Watanabe S, Hashimoto E, Ikejima K, Uto H, Ono M, Sumida Y, Seike M, Takei Y, Takehara T, Tokushige K, Nakajima A, Yoneda M, Saibara T, Shiota G, Sakaida I, Nakamuta M, Mizuta T, Tsubouchi H, Sugano K, Shimosegawa T.
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Journal Title
Hepatol Res.
Volume: 45
Issue: 4
Pages: 363-377
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Pilot study of liraglutide effects in nonalcoholic steatohepatitis and nonalcoholic fatty liver disease with glucose intolerance in Japanese patients (LEAN-J).2014
Author(s)
Eguchi Y, Kitajima Y, Hyogo H, Takahashi H, Kojima M, Ono M, Araki N, Tanaka K, Yamaguchi M, Matsuda Y, Ide Y, Otsuka T, Ozaki I, Ono N,3 Eguchi T, Anzai K, and Japan Study Group for NAFLD (JSG-NAFLD)
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Journal Title
Hepatol Res
Volume: 45
Issue: 3
Pages: 269-78
DOI
Related Report
Peer Reviewed
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[Journal Article] Simple scoring system for predicting cirrhosis in nonalcoholic fatty liver disease.2014
Author(s)
Kessoku T, Ogawa Y, Yoneda M, Imajo K, Sumida Y, Eguchi Y, Fujii H, Hyogo H, Ono M, Suzuki Y, Kawaguchi T, Chayama K, Tanaka S, Fujimoto K, Anzai K, Saibara T, Sata M, Itoh Y, Nakajima A, Okanoue T
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Journal Title
World J Gastroenterol
Volume: 20(29)
Issue: 29
Pages: 10108-10114
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Type 2 diabetes mellitus is associated with the fibrosis severity in patients with nonalcoholic fatty liver disease in a large retrospective cohort of Japanese patients.2014
Author(s)
Nakahara T, Hyogo H, Yoneda M, Sumida Y, Eguchi Y, Fujii H, Ono M, Kawaguchi T, Imajo K, Aikata H, Tanaka S, Kanemasa K, Fujimoto K, Anzai K, Saibara T, Sata M, Nakajima A, Itoh Y, Chayama K, Okanoue T
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Journal Title
J Gastroenterol
Volume: 49(11)
Issue: 11
Pages: 1477-1484
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] The association of insomnia with gastroesophageal reflux symptoms in biopsy-proven nonalcoholic fatty liver disease.2014
Author(s)
Taketani H, Sumida Y, Tanaka S, Imajo K, Yoneda M, Hyogo H, Ono M, Fujii H, Eguchi Y, Kanemasa K, Chayama K, Itoh Y, Yoshikawa T, Saibara T, Fujimoto K, Nakajima A
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Journal Title
J Gastroenterol
Volume: 49(7)
Issue: 7
Pages: 1163-1174
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Evaluation of Ki-67 index in EUS-FNA specimens for the assessment of malignancy risk in pancreatic neuroendocrine tumors.2014
Author(s)
Hasegawa T, Yamao K, Hijioka S, Bhatia V, Mizuno N, Hara K, Imaoka H, Niwa Y, Tajika M, Kondo S, Tanaka T, Shimizu Y, Kinoshita T, Kohsaki T, Nishimori I, Iwasaki S, Saibara T, Hosoda W, Yatabe Y
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Journal Title
Endoscopy
Volume: 46(1)
Issue: 01
Pages: 32-38
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Multicenter validation study of anti-programmed cell death-1 antibody as a serological marker for type 1 autoimmune hepatitis.2014
Author(s)
Miyake Y, Yamamoto K, Matsushita H, Abe M, Takahashi A, Umemura T, Tanaka A, Nakamuta M, Nakamoto Y, Ueno Y, Saibara T, Takikawa H, Yoshizawa K, Ohira H, Zeniya M, Onji M, Tsubouchi H; Intractable Liver and Biliary Diseases Study Group of Japan
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Journal Title
Hepatol Res.
Volume: in press
Issue: 13
Pages: 1299-1307
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Autoantibody status and histological variables influence biochemical response to treatment and long-term outcomes in Japanese patients with primary biliary cirrhosis.2014
Author(s)
Nakamura M, Kondo H, Tanaka A, Komori A, Ito M, Yamamoto K, Ohira H, Zeniya M, Hashimoto E, Honda M, Kaneko S, Ueno Y, Kikuchi K, Shimoda S, Harada K, Arai K, Miyake Y, Abe M, Taniai M, Saibara T, Sakisaka S, Takikawa H, Onji M, Tsubouchi H, Nakanuma Y, Ishibashi H.
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Journal Title
Hepatol Res.
Volume: -
Issue: 8
Pages: 846-855
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Safety and efficacy of image-guided enzyme-targeting radiosensitization and intraoperative radiotherapy for locally advanced unresectable pancreatic cancer.2014
Author(s)
Nishioka A, Ogawa Y, Miyatake K, Tadokoro M, Nogami M, Hamada N, Kubota K, Kariya S, Kohsaki T, Saibara T, Okabayashi T, Hanazaki K
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Journal Title
Oncol Lett
Volume: 8
Pages: 404-408
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] Bofutsushosan, a Japanese herbal (Kampo) medicine, attenuates progression of nonalcoholic steatohepatitis in mice2013
Author(s)
Masafumi Ono, Mitsunari Ogasawara, Akira Hirose, Sachiko Mogami, Nobuhiro Ootake, Kosuke Aritake, Takuma Higuchi, Nobuto Okamoto, Shuji Sakamoto, Masahiro Yamamoto, Yoshihiro Urade, Toshiji Saibara, Jude A. Oben.
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Journal Title
Journal of Gastroenterology
Volume: 49(6)
Issue: 6
Pages: 1065-1173
DOI
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Peer Reviewed / Open Access
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[Presentation] Correlation between glucose intolerance and histological severity in non-alcoholic fatty liver disease.2014
Author(s)
Ohmi S, Ono M, Nishi Y, Hirano S, Tsugita S, Takata H, Yoshimura K, Mori S, Terada Y, Saibara T, Fujimoto S
Organizer
American Diabetes Association 74th Scientific Sessions 2014
Place of Presentation
San Francisco, US
Year and Date
2014-06-13 – 2014-06-17
Related Report
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[Presentation] 基調講演2014
Author(s)
西原利治
Organizer
第50回日本肝癌研究会
Place of Presentation
国立京都国際会館(京都)
Year and Date
2014-06-05 – 2014-06-06
Related Report
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