The regulatory role of Nrf2 in pathogenesis and carcinogenesis of NASH using gene rescued mice
Project/Area Number |
26293297
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Research Category |
Grant-in-Aid for Scientific Research (B)
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Allocation Type | Partial Multi-year Fund |
Section | 一般 |
Research Field |
Digestive surgery
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Research Institution | University of Tsukuba |
Principal Investigator |
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Co-Investigator(Kenkyū-buntansha) |
柳川 徹 筑波大学, 医学医療系, 准教授 (10312852)
酒井 俊 筑波大学, 医学医療系, 講師 (30282362)
磯辺 智範 筑波大学, 医学医療系, 准教授 (70383643)
蕨 栄治 筑波大学, 医学医療系, 講師 (70396612)
正田 純一 筑波大学, 医学医療系, 教授 (90241827)
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Co-Investigator(Renkei-kenkyūsha) |
YAMAMOTO Masayuki 東北大学, 医学系研究科, 教授 (50166823)
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Project Period (FY) |
2014-04-01 – 2017-03-31
|
Project Status |
Completed (Fiscal Year 2016)
|
Budget Amount *help |
¥15,990,000 (Direct Cost: ¥12,300,000、Indirect Cost: ¥3,690,000)
Fiscal Year 2016: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2015: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2014: ¥7,930,000 (Direct Cost: ¥6,100,000、Indirect Cost: ¥1,830,000)
|
Keywords | 生活習慣病 / 脂肪性肝炎 / 肝癌 / 遺伝子改変マウス / 病態生理 / 肥満関連肝疾患 / 転写因子 / 遺伝子レスキューマウス / 肝発癌 |
Outline of Final Research Achievements |
We generated Sqstm1 and Nrf2 double knockout (DKO) mice as the noble NASH animal model. We revealed the mechanism for the development of steatohepatitis in DKO mice as follows: (1) Deficiency of Nrf2 led to hypersensitivity to endotoxin of Kupffer cells and resulted in the inflammatory response in the DKO livers. (2) Acceleration of intestinal permeability which was caused by down-regulation of Zo-1 and Claudin1 in Nrf2 deficiency and increased endotoxin from intestinal microbiota by Sqstm1 deficiency led to an overload of serum endotoxin. (3) These hyper-endotoxemia drove inflammatory signaling in livers directly, and also led to inflammation of adipose tissue. (4) These enhanced inflammatory signaling could cause progression of steatohepatitis in DKO livers. We plan to compare DKO and Nrf2 gene rescued mice, and explore the detail of the mechanism for development of NASH and the carcinogenesis in contribution of each organ in the near future.
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Report
(4 results)
Research Products
(83 results)
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[Journal Article] 陽子線による放射線性十二指腸炎からの出血に対してアルゴンプラズマ凝固法が有用であった1例2016
Author(s)
高木 薫子, 長谷川 直之, 新里 悠輔, 山浦 正道, 小松 義希, 俣野 大介, 岩井 健太郎, 江南 ちあき, 石毛 和紀, 福田 邦明, 奈良坂 俊明, 金子 剛, 安部井 誠人, 兵頭 一之介, 溝上 裕士
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Journal Title
Progress of Digestive Endoscopy
Volume: 89
Pages: 106-107
NAID
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Author(s)
田地 広明, 會田 有香, 大澤 翔, 北沢 晴奈, 中嶋 真之, 渡辺 裕子, 塩澤 利博, 中澤 健介, 増子 裕典, 小川 良子, 際本 拓未, 松野 洋輔, 川口 未央, 森島 祐子, 坂本 透, 家城 隆次, 檜澤 伸之, 石毛 和紀, 坂下 信悟, 野口 雅之, 後藤 行延, 佐藤 幸夫, 関根 郁夫
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Journal Title
肺癌
Volume: 56
Pages: 321-322
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[Journal Article] p62 modulates the intrinsic signaling of UVB-induced apoptosis.2016
Author(s)
Ito S, Kimura S, Warabi E, Kawachi Y, Yamatoji M, Uchida F, Ishibashi-Kanno N, Yamagata K, Hasegawa S, Shoda J, Tabuchi K, Sakai S, Bukawa H, Sekido M, Yanagawa T.
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Journal Title
Journal of Dermatological Science
Volume: 83
Issue: 3
Pages: 226-233
DOI
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Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Wisteria floribunda Agglutinin-Sialylated Mucin Core Polypeptide 1 is a Sensitive Biomarker for Biliary Tract Carcinoma and Intrahepatic Cholangiocarcinoma: A Multicenter Study.2016
Author(s)
Shoda J, Matsuda A, Shida T, Yamamoto M, Nagino M, Tsuyuguchi T, Yasaka T, Tazuma S, Uchiyama K, Unno M, Ohkohchi N, Nakanuma Y, Kuno A, Narimatsu H.
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Journal Title
J Gastroenterol
Volume: 52
Issue: 2
Pages: 218-228
DOI
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Peer Reviewed / Open Access
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[Journal Article] Acceleration training for management of non-alcoholic fatty liver disease: a pilot study.2014
Author(s)
Oh S, Shida T, Onozuka T, Maruyama T, Eguchi K, Isobe T, Okamoto Y, Someya N, Tanaka K, Tozawa A, Arai E, Shoda J.
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Journal Title
Ther Clin Risk Manag
Volume: 10
Pages: 925-936
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Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] Peroxidoxin I plays a ptotective role against UVA irradiation through reduction of oxidative stress.2014
Author(s)
Ito T, Kimura S, Seto K, Warabi E, Kawauchi Y, Shoda J, Tabuchi K, Yamagata K, Hasegawa S, Bukawa H, Ishii T, Yanagawa T.
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Journal Title
J Dermatol Sci
Volume: 74
Pages: 9-17
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[Journal Article] Expression of N-acetylglucosaminyltransferase V in the subserosal layer correlates with postsurgical survival of pathological tumor stage 2 carcinoma of the gallbladder.2014
Author(s)
Onuki K, Sugiyama H, Ishige K, Kawamoto T, Ota T, Ariizumi S, Yamato M, Kadota S, Takeuchi K, Ishikawa A, Onodera M, Onizawa K, Yamamoto M, Miyoshi E, Shoda J.
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Journal Title
J Gastroenterol
Volume: 49
Pages: 702-714
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[Presentation] ダビガトランによる剥離性食道炎を伴った食道表在癌の1例2016
Author(s)
野中 遥奈, 田島 大樹, 廣瀬 優, 山浦 正道, 菅沼 大輔, 佐藤 雅志, 内田 優一, 山田 武史, 山本 祥之, 長谷川 直之, 石毛 和紀, 金子 剛, 鈴木 英雄, 奈良坂 俊明, 福田 邦明, 安部井 誠人, 兵頭 一之介, 溝上 裕士
Organizer
第103回日本消化器内視鏡学会関東支部会
Place of Presentation
シェーンバッハ・サボー(東京都・千代田区)
Year and Date
2016-12-17
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[Presentation] 陽子線による放射線性十二指腸炎からの出血に対してアルゴンプラズマ凝固法(APC)が有用であった一例2016
Author(s)
高木 薫子, 長谷川 直之, 新里 悠輔, 山浦 正道, 小松 義希, 俣野 大介, 岩井 健太郎, 江南 ちあき, 石毛 和紀, 福田 邦明, 奈良坂 俊明, 金子 剛, 安部井 誠人, 溝上 裕士, 兵頭 一之介
Organizer
第102回日本消化器内視鏡学会関東支部会
Place of Presentation
シェーンバッハ・サボー(東京都・千代田区)
Year and Date
2016-12-17
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[Presentation] 抗凝固薬による薬剤性食道炎の検討2016
Author(s)
奈良坂 俊明, 溝上 裕士, 俣野 大介, 岩井 健太郎, 江南 ちあき, 寺崎 正彦, 圷 大輔, 長谷川 直之, 石毛 和紀, 金子 剛, 鈴木 英雄, 福田 邦明, 松井 裕史, 兵頭 一之介
Organizer
第92回日本消化器内視鏡学会総会
Place of Presentation
神戸国際会議場(兵庫県・神戸市)
Year and Date
2016-11-03
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[Presentation] 胆道癌に関連した後天性血友病の2例2016
Author(s)
佐藤 雅志, 長谷川 直之, 松田 健二, 橋本 真治, 石毛 和紀, 福田 邦明, 西 雅明, 川西 宣裕, 松木 康彦, 安部井 誠人, 溝上 裕士, 兵頭 一之介
Organizer
胆道
Place of Presentation
横浜プリンスホテル(神奈川県・横浜市)
Year and Date
2016-09-29
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[Presentation] Clinical benefits of acceleration training for management of obese subjects with non-alcoholic fatty liver disease.2014
Author(s)
Oh S, Shida T, Sawai A, Eguchi K, Maruyama T, So T, Komine S, Horie M, Akiyama K, Tanaka K, Shoda J
Organizer
INCHEON ASIAN GAMES INTERNATIONAL SPORT SCIENCE CONGRESS (Korea)
Place of Presentation
Korea
Year and Date
2014-08-20 – 2014-08-22
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