Analysis of pathogenic mechanism in novel NASH model mice

• Project/Area Number: 26460485
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Experimental pathology
• Research Institution: University of Tsukuba
• Principal Investigator: Warabi Eiji 筑波大学, 医学医療系, 講師 (70396612)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: NASH

Outline of Final Research Achievements

The aim of this study is to elucidate the pathological mechanism of NASH in p62:Nrf2 double knockout mice that were recently developed by our group and found that they showes a very similar phenotype to human NASH. It is suggested that in DKO mice, intestinal epithelial permeability is accelerated, resulting in high endotoxinemia, causing inflammation in the liver. It is considered that these defects are main reasons for NASH onset.

Research Products

• [Journal Article] Autophagy controls centrosome number by degrading Cep63. (2016)
  • Author(s): Watanabe Y, Honda S, Konishi A, Satoko Arakawa S, Murohashi M, Yamaguchi H, Torii S, Tanabe M, Tanaka S, Warabi E, Shimizu S.
  • Journal Title: Nature Communications Volume: 7 Issue: 1 Pages: 13508-13508
  • DOI: 10.1038/ncomms13508
  • NAID: 120007129257
  • Peer Reviewed / Open Access
• [Journal Article] Detailed Analysis of the Binding Mode of Vanilloids to Transient Receptor Potential Vanilloid Type I (TRPV1) by a Mutational and Computational Study. (2016)
  • Author(s): Ohbuchi K, Mori Y, Ogawa K, Warabi E, Yamamoto M, Hirokawa T.
  • Journal Title: PLoS One Volume: 11 Issue: 9 Pages: e0162543-e0162543
  • DOI: 10.1371/journal.pone.0162543
  • NAID: 120007129393
  • Peer Reviewed / Open Access
• [Journal Article] Ignavine: a novel allosteric modulator of the μ opioid receptor. (2016)
  • Author(s): Ohbuchi K, Miyagi C, Suzuki Y, Mizuhara Y, Mizuno K, Omiya Y, Yamamoto M, Warabi E, Sudo Y, Yokoyama A, Miyano K, Hirokawa T, Uezono Y.
  • Journal Title: Scientific Reports Volume: 6 Issue: 1 Pages: 31748-31748
  • DOI: 10.1038/srep31748
  • NAID: 120007129422
  • Peer Reviewed / Open Access
• [Journal Article] Functional links between SQSTM1 and ALS2 in the pathogenesis of ALS: Cumulative impact on the protection against mutant SOD1-mediated motor dysfunction in mice (2016)
  • Author(s): Hadano, S., Mitsui, S., Pan, L., Otomo, A., Kubo, M., Sato, K., Ono, S., Onodera, W., Abe, K., Koike, M., Uchiyama, Y., Aoki, M., Warabi, E., Yamamoto, M., Ishii, T., Yanagawa, T., Shang, HF., Yoshii, F
  • Journal Title: Hum. Mol. Genet. Volume: 25 Issue: 15 Pages: 3321-3340
  • DOI: 10.1093/hmg/ddw180
  • Peer Reviewed / Open Access / Int'l Joint Research
• [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.
  • Journal Title: Journal of Dermatological Science Volume: 83 Issue: 3 Pages: 226-233
  • DOI: 10.1016/j.jdermsci.2016.05.005
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] The role of peroxiredoxin I in cisplatin-induced ototoxicity. (2016)
  • Author(s): Le Q, Tabuchi K, Warabi E, Hara A.
  • Journal Title: Auris Nasus Larynx Volume: 44 Issue: 2 Pages: 205-212
  • DOI: 10.1016/j.anl.2016.06.001
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] p62/Sequestosome1の生理機能 (2014)
  • Author(s): 蕨栄治
  • Journal Title: 生化学 Volume: 86 Pages: 783-787
  • NAID: 40020314244
  • Open Access
• [Presentation] p62:Nrf2遺伝子二重欠損マウスの肝蔵、内臓脂肪、腸内環境の解析よりみた NASH発症機序の解明 (2016)
  • Author(s): 秋山健太郎、蕨栄治、正田純一
  • Organizer: 第41回日本肝臓学会東部会
  • Place of Presentation: 京王プラザホテル（東京・新宿区）
  • Year and Date: 2016-12-08
• [Presentation] 継続的な運動はKupffer細胞の異物貪食能の増大により、菌体内毒素(LPS)のクリアランスを増大させ、LPS刺激による炎症応答を低下させる (2016)
  • Author(s): 小峰昇一、秋山健太郎、蕨栄治、正田純一
  • Organizer: 第41回日本肝臓学会東部会
  • Place of Presentation: 京王プラザホテル（東京・新宿区）
  • Year and Date: 2016-12-08
• [Presentation] 継続的な運動負荷は菌体内毒素（LPS）クリアランスを増大させ、LPS刺激による炎症応答を低下させる (2016)
  • Author(s): 小峰昇一、秋山健太郎、蕨栄治、正田純一
  • Organizer: 第71回日本体力医学会大会
  • Place of Presentation: いわて県民情報交流センター（岩手・盛岡市）
  • Year and Date: 2016-09-24
• [Presentation] 非アルコール性脂肪性肝炎(NASH)自然発症マウスにおける Kupffer 細胞の表現形質の変化と発症機序との関連性 (2016)
  • Author(s): 秋山健太郎、蕨栄治、正田純一
  • Organizer: 102回日本消化器病学会総会
  • Place of Presentation: 京王プラザホテル（東京・新宿区）
  • Year and Date: 2016-04-21
• [Presentation] p62: Nrf2遺伝子二重欠損マウスは血清中エンドトキシンが増加し，脂肪性肝炎を発症する (2015)
  • Author(s): 秋山健太郎，蕨 栄治，岡田浩介，正田 純一
  • Organizer: 第38回日本分子生物学会年会・第88回日本生化学大会合同大会
  • Place of Presentation: 神戸ポートアイランド（神戸）
  • Year and Date: 2015-12-01
• [Presentation] ASH自然発症モデルマウスの腸内環境よりみた疾病病態の解析と発症機序の解明 (2015)
  • Author(s): 秋山健太郎, 池内美穂, 蕨 栄治, 正田純一
  • Organizer: 日本消化器関連学会週間(JDDW)
  • Place of Presentation: グランドプリンスホテル新高輪（東京）
  • Year and Date: 2015-10-08
• [Presentation] 非アルコール性脂肪性肝炎自然発症モデルマウスにおける腸内環境の変化とNASH発症機序の解明 (2015)
  • Author(s): 秋山健太郎，池内美穂，青山希，蕨 栄治，正田純一
  • Organizer: 第51回日本肝臓学会
  • Place of Presentation: ホテル日航熊本（熊本）
  • Year and Date: 2015-05-21
• [Presentation] 生活習慣病とp62/Sqstm1 (2014)
  • Author(s): 蕨栄治
  • Organizer: 臨床フリーラジカル会議
  • Place of Presentation: 京都・烟河
  • Year and Date: 2014-12-05 – 2014-12-06
  • Invited
• [Presentation] ノックアウトマウスから見るp62/Sqstm1の分子機能 (2014)
  • Author(s): 蕨栄治
  • Organizer: 日本酸化ストレス学会
  • Place of Presentation: 同志社大学
  • Year and Date: 2014-09-04 – 2014-09-05
  • Invited