Role of innate immune system in the regulation of hepatic metabolism and pathogenesis of steatohepatitis
| Project/Area Number |
21590859
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Gastroenterology
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| Research Institution | Juntendo University |
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Principal Investigator |
IKEJIMA Kenichi 順天堂大学, 医学(系)・研究科(研究院), 准教授 (20317382)
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| Co-Investigator(Kenkyū-buntansha) |
YAMASHINA Shunhei 順天堂大学, 医学部, 准教授 (30338412)
KON Kazyyoshi 順天堂大学, 医学部, 准教授 (30398672)
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| Co-Investigator(Renkei-kenkyūsha) |
TAKEDA Kazuyoshi 順天堂大学, 医学部, 准教授 (80272821)
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| Project Period (FY) |
2009 – 2011
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| Project Status |
Completed (Fiscal Year 2011)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2011: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2010: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2009: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
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| Keywords | 非アルコール性脂肪肝炎(NASH) / 自然免疫 / メタボリックシンドローム / NKT細胞 / 肝線維化 / 肝再生 / NK細胞 / CD1d / アディポカイン / チアゾリジン系誘導体 |
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| Research Abstract |
Recent lines of evidence support the hypothesis that innate immune system plays a pivotal role in pathogenesis of nonalcoholic steatohepatitis. In this study, we found that KK-Ay mice, which present metabolic syndrome-like phenotypes, show progressive depletion of hepatic natural killer T(NKT) cells in combination with functional abnormalities. On the other hand, CD1d-knockout(KO) mice, in which NKT cells are systemically defective, develop minimal hepatic fibrosis caused by thioacetamide. Further, deprivation of NK and NKT cells using an NK1.1 antibody resulted in impaired regenerative response following partial hepatectomy. Collectively, these findings indicate that hepatic NKT cells are required for tissue-repair and fibrogenic responses in the liver.
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Report
(4 results)
Research Products
(104 results)
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[Journal Article] Inhibition of hepatitis C virus replication by chloroquine targeting virus-associated autophagy2010
Author(s)
Mizui T, Yamashina S, Tanida I, Takei Y, Ueno T, Sakamoto N, Ikejima K, Kitamura T, Enomoto N, Sakai T, Kominami E, Watanabe S
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Journal Title
J Gastroenterol
Volume: 45(2)
Pages: 195-203
NAID
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Peer Reviewed
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[Journal Article]2010
Author(s)
池嶋健一, 渡辺純夫
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Journal Title
第8章 肝疾患 10. 脂肪肝, 脂肪性肝炎. 医学スーパーラーニングシリーズ 消化器内科学(渡辺純夫編)(シュプリンガー・ジャパン)
Pages: 254-258
Related Report
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[Journal Article] Hepatic sinusoidal cells in health and disease : update from the 14th International Symposium2009
Author(s)
Smedsrod B, Le Couteur D, Ikejima K, Jaeschke H, Kawada N, Naito M, Knolle P, Nagy L, Senoo H, Vidal-Vanaclocha F, Yamaguchi N
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Journal Title
Liver Int
Volume: 29(4)
Pages: 490-501
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[Presentation] Loss of parkin impairs liver regeneration2011
Author(s)
Fukada H, Yamashina S, Izumi K, Nakadera E, Fukuo Y, Uchiyama A, Kon K, Ikejima K, Watanabe S
Organizer
Poster Session, The Liver Meeting 2011(Annual Meeting of American Association for Study of Liver Diseases)
Place of Presentation
San Francisco, CA, USA
Year and Date
2011-11-06
Related Report
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[Presentation] Mice depleting natural killer T cells are more susceptible to dietary-induced steatohepatitis, Selected Oral Presentation 102011
Author(s)
Ikejima K, Yamagata H, Arai K, Ishikawa S, Hosoya S, Kon K, Yamashina S, Suzuki S, Takeda K, Watanabe S
Organizer
18th International Symposium on Cells of the Hepatic Sinusoid(Biannual Meeting of International Society for Hepatic Sinusoidal Research)
Place of Presentation
Florence, Italy
Year and Date
2011-09-22
Related Report
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[Presentation] Imaired liver regeneration after partial hepatectomy in mice depleting NK and NKT cells2011
Author(s)
Hosoya S, Ikejima K, Arai K, Aoyama T, Kon K, Ishikawa S, Yamagata H, Yamashina S, Suzuki S, Takeda K, Watanabe S
Organizer
Poster Session, 18th International Symposium on Cells of the Hepa Sin usoid(Biannual Meeting of International Society for Hepatic Sinusoidal Research)
Place of Presentation
Florence, Italy
Year and Date
2011-09-22
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[Presentation] Hepatic NKT and NK cells regulate liver reg hep atectomy in mice2010
Author(s)
Hosoya S, Ikejima K, Aoyama T, Ishikawa S, Yamagata H, Kon K, Yamashina S, Takeda K, Watanabe S
Organizer
Poster Session, The Liver Meeting 2010(Annual Meeting of American Association for Study of Liver Diseases)
Place of Presentation
Boston, MA, USA
Year and Date
2010-11-03
Related Report
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[Presentation] Depletion of natural killer T cells increases the susceptibility to dietary-induced steatohepatitis in mice2010
Author(s)
Ikejima K, Yamagata H, Arai K, Ishikawa S, Hosoya S, Kon K, Yamashina S, Takeda K, Watanabe S
Organizer
Poster Session, The Liver Meeting 2010(Annual Meeting of American Association for Study of Liver Diseases)
Place of Presentation
Boston, MA, USA
Year and Date
2010-11-01
Related Report
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[Presentation] Trans-fatty acid induces apoptosis of hepatocytes by enhancement of oxidative stress in steatotic liver of KK-Ay mice2010
Author(s)
Kon K, Ikejima K, Saito H, Ishikawa S, Hosoya S, Arai K, Okumura K, Yamashina S, Watanabe S
Organizer
Poster Session, The Liver Meeting 2010(Annual Meeting of American Association for Study of Liver Diseases)
Place of Presentation
Boston, MA, USA
Year and Date
2010-11-01
Related Report
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[Presentation] Contribution of CD1d-restricted natural killer T cells to xenobiotics-induced hepatic inflammation and fibrogenesis in mice2010
Author(s)
Ikejima K, Ishikawa S, Yamagata H, Aoyama T, Kon K, Arai K, Takeda K, Watanabe S
Organizer
Session II. Steatohepatitis-II(Oral presentation), 15th International Symposium on Cells of the Hepatic Sinusoid
Place of Presentation
Pasadena, CA, USA
Year and Date
2010-08-29
Related Report
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[Presentation] Loss of autophagy enhances acetaminophen-induced liver injury2010
Author(s)
Igusa Y, Yamashina S, Izumi K, Fukada H, Mikirai A, Inami Y, Kon K, Ikejima K, Watanabe S
Organizer
AASLD Poster Session, Digestive Disease Week(DDW)
Place of Presentation
New Orleans, LA, USA
Year and Date
2010-05-02
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[Presentation] High-carbohydrate diet containing trans-fatty acid induces severe steatohepatitis via the enhancement of endoplasmic reticulum stress in KK-Ay mice2010
Author(s)
Saito H, Kon K, Ishikawa S, Hosoya S, Arai K, Takashima M, Yamashina S, Ikejima K, Watanabe S
Organizer
Poster Session, The 45th annual meeting of the European Association for the Study of the Liver
Place of Presentation
Vienna, Austria
Year and Date
2010-04-16
Related Report
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[Presentation] Impaired hepatic innate responses involving NKT cells in obese diabetic KK-Ay mice2010
Author(s)
Yamagata H, Ikejima K, Ishikawa S, Aoyama T, Kon K, Arai K, Takeda K, Watanabe S
Organizer
Poster Session I Steatohepatitis-NASH, 15^<th> Int ernational Symposium on Cells of International Symposium on Cells of the Hepatic Sinusoid
Place of Presentation
Pasadena, CA, USA
Related Report
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[Presentation] 脂肪性肝炎形成における肝細胞内貯蔵鉄の役割-マウス初代培養肝細胞を用いた検討-ワークショップ1, NASH・NAFLDの礎2009
Author(s)
今一義, 池嶋健一, 青山友則, 山形寿文, 内山明, 高島基樹, 石川幸子, 柳沼礼子, 山科俊平, 鈴木聡子, 渡辺純夫
Organizer
第45回日本肝臓学会総会
Place of Presentation
神戸
Year and Date
2009-06-04
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