Novel roles of CYLD in the molecular pathogenesis of intractable diseases

• Project/Area Number: 20890167
• Research Category: Grant-in-Aid for Young Scientists (Start-up)
• Allocation Type: Single-year Grants
• Research Field: Biological pharmacy
• Research Institution: Kumamoto University
• Principal Investigator: JONO Hirofumi Kumamoto University, 大学院・生命科学研究部, 講師 (40515483)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥3,302,000 (Direct Cost: ¥2,540,000、Indirect Cost: ¥762,000); Fiscal Year 2009: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2008: ¥1,742,000 (Direct Cost: ¥1,340,000、Indirect Cost: ¥402,000)
• Keywords: CYLD / 肺線維症 / 慢性閉塞性肺疾患 / 家族性アミロイドポリニューロパチー / 脱ユピキチン化酵素 / 遺伝性疾患 / 細菌感染症

Research Abstract

Tumor suppressor CYLD has been recently shown to play important roles in the pathogenesis of various intractable diseases. In the present study, we focused on the CYLD-related diseases (1. lung fibrosis, 2. chronic obstructive pulmonary disease, 3. familial amyloidotic polyneuropathy) and revealed that CYLD acted as a deubiquitinase and involved in various diseases by suppressing intracellular signaling, such as TGFβ signal and NF-κB signal to regulate the disease-related gene expression.

Research Products

• [Journal Article] Cyclodextrin, a novel therapeutic tool for suppressing amyloidogenic transthyretin misfolding in transthyretin-related amyloidosis. (2011)
  • Author(s): Jono H, Anno T, Motoyama K, Misumi Y, Tasaki T, Oshima T, Mori Y, Mizuguchi M, Ueda M, Shono M, Obayashi K, Arima H, Ando Y.
  • Journal Title: Biochem J in press.
  • Peer Reviewed
• [Journal Article] Loss of functional albumin triggers acceleration of transthyretin amyloid fibril formation in familial amyloidotic polyneuropathy. (2011)
  • Author(s): Kugimiya T, Jono H, Saito S, Maruyama M, Kadowaki D, Misumi Y, Hoshii Y, Tasaki T, Su Y, Ueda M, Obayashi K, Shono M, Otagiri M, Ando Y.
  • Journal Title: Lab Invest in press
  • Peer Reviewed
• [Journal Article] Wild-type transthyretin-derived amyloidosis in various ligaments and tendons. (2011)
  • Author(s): Sueyoshi T, Ueda M, Jono H, Irie H, Sei A, Ide J, Ando Y, Mizuta H.
  • Journal Title: Hum Pathol in press
  • Peer Reviewed
• [Journal Article] Amyloid neuropathy in a younger domino liver transplanted recipient. (2011)
  • Author(s): Obayashi K, Yamashita T, Tasaki M, Ueda M, Shono M, Jono H, Ohshima T, Ohya Y, Asonuma K, Inomata Y, Ando Y.
  • Journal Title: Muscle Nerve 43 Pages: 449-450
  • Peer Reviewed
• [Journal Article] Hepatic Stellate Cells Accelerate the Malignant Behavior of Cholangiocarcinoma Cells. (2011)
  • Author(s): Okabe H, Beppu T, Hayashi H, Ishiko T, Masuda T, Otao R, Horlad H, Jono H, Ueda M, Phd SS, Ando Y, Baba H.
  • Journal Title: Ann Surg Oncol 18 Pages: 1175-1184
  • Peer Reviewed
• [Journal Article] Ca^2+/calmodulin-stimulate PDE1 regulate the beta-catenin/TCF signaling through PP2A B56 gamma subunit in proliferating vascular smooth muscle cells. (2010)
  • Author(s): Jeon KI, Jono H, Miller CL, Cai Y, Lim S, Liu X, Gao P, Abe J, Li JD, Yan C.
  • Journal Title: FEBS J 277 Pages: 5026-5039
  • Peer Reviewed
• [Journal Article] Trans Soluble amyloidgenic enhancing factor Circulating via exosomes. (2010)
  • Author(s): Tasaki M, Ueda M, Ochiai S, Tanabe Y, Murata S, Su Y, Shinriki S, Jono H, Shono M, Obayashi K, Nakamura T, Yamada M, Ando Y.
  • Journal Title: Biochem Biophys Res Commun 400 Pages: 559-562
  • Peer Reviewed
• [Journal Article] Vinpocetine inhibits NF-kappaB dependent inflammation via an IKK-dependent but PDE-independent mechanism. (2010)
  • Author(s): Jeon KI, Xu X, Aizawa T, Lim JH, Jono H, Kwon DS, Abe J, Berk BC, Li JD, Yan C.
  • Journal Title: Proc Natl Acad Sci USA 107 Pages: 9795-9800
  • Peer Reviewed
• [Journal Article] In Vitro and In Vivo Gene Delivery Mediated by Lactosylated Dendrimer/α-Cyclodextrin Conjugates (G2) into Hepatocytes. (2010)
  • Author(s): Arima H, Yamashita S, Mori Y, Hayashi Y, Motoyama K, Hattori K, Takeuchi T, Jono H, Ando Y, Hirayama F, Uekama K.
  • Journal Title: Journal of Controlled Release 146 Pages: 106-117
  • Peer Reviewed
• [Journal Article] Differential regulation of Streptococcus pneumoniae-induced human MUC5AC mucin expression through distinct MAPK pathways. (2009)
  • Author(s): Lim JH, Kim HJ, Komatsu K, Ha U, Huang Y, Jono H, Kweon SM, Lee J, Xu X, Zhang GS, Shen H, Kai H, Zhang W, Xu H, Li JD.
  • Journal Title: Am J Transl Res 8 Pages: 300-311
  • Peer Reviewed
• [Journal Article] Chain reaction of amyloid fibril formation with induction of basement membrane in familial amyloidotic polyneuropathy. (2009)
  • Author(s): Misumi Y, Ando Y, Ueda M, Obayashi K, Jono H, Su Y, Yamashita T, Uchino M.
  • Journal Title: J Pathol 219 Pages: 481-490
  • Peer Reviewed
• [Journal Article] Humanized anti-interleukin-6 receptor antibody suppresses tumor angiogenesis and in vivo growth of human oral squamous cell carcinoma. (2009)
  • Author(s): Shinriki S, Jono H, Ota K, Ueda M, Kudo M, Ota T, Oike Y, Endo M, Ibusuki M, Hiraki A, Nakayama H, Yoshitake Y, Shinohara M, Ando Y.
  • Journal Title: Clin Cancer Res 15 Pages: 5426-5434
  • Peer Reviewed
• [Journal Article] SELDI-TOF mass spectrometry evaluation of variant transthyretins for diagnosis and pathogenesis of familial amyloidotic polyneuropathy. (2009)
  • Author(s): Ueda M, Misumi Y, Mizuguchi M, Nakamura M, Yamashita T, Sekijima Y, Ota K, Shinriki S, Jono H, Ikeda S, Suhr OB, Ando Y.
  • Journal Title: Clin Chem. 55 Pages: 1223-1227
  • Peer Reviewed
• [Journal Article] Synergistic induction of nuclear factor-kappaB by transforming growth factor-beta and tumour necrosis factor-alpha is mediated by protein kinase A-dependent RelA acetylation. (2009)
  • Author(s): Ishinaga H, Jono H, Lim JH, Komatsu K, Xu X, Lee J, Woo CH, Xu H, Feng XH, Chen LF, Yan C, Li JD.
  • Journal Title: Biochem J. 417 Pages: 583-591
  • Peer Reviewed
• [Journal Article] SELDI-TOF MS evaluation of variant transthyretins for diagnosis and pathogenesis of familial amyloidotic polyneuropathy. (2009)
  • Author(s): Ueda M(Jono H, 9^<th>)
  • Journal Title: Clinical Chemistry (in press)
  • Peer Reviewed
• [Journal Article] Glucocorticoids inhibit nontypeable Haemophilus influenzae-induced MUC5AC mucin expression via MARK phosphatase-l-dependent inhibition of p38 MAPK. (2009)
  • Author(s): Komatsu K(Jono H, equally contributed)
  • Journal Title: Biochemical Journal 417 Pages: 583-591
  • Peer Reviewed
• [Journal Article] Glucocorticoids inhibit nontypeable Haemophilus influenza induced MUC5AC mucin expression via MAPK phosphatase-1 dependent inhibition of p38 MAPK. (2008)
  • Author(s): Komatsu K, Jono H, Lim JH, Imasato A, Xu H, Kai H, Yan C, Li JD.
  • Journal Title: Biochem Biophys Res Commun. 19 Pages: 763-768
  • Peer Reviewed
• [Journal Article] Tumor suppressor cylindromatosis acts as a negative regulator for Streptococcus pneumoniae-induced NFAT signaling. (2008)
  • Author(s): Koga T, Lim JH, Jono H, Ha UH, Xu H, Ishinaga H, Morino S, Xu X, Yan C, Kai H, Li JD.
  • Journal Title: J Biol Chem 283 Pages: 12546-12554
  • Peer Reviewed
• [Journal Article] Midkine as a prognostic biomarker in oral squamous cell carcinoma. (2008)
  • Author(s): Ota K, Fujimori H, Ueda M, Shiniriki S, Kudo M, Jono H, Fukuyoshi Y, Yamamoto Y, Sugiuchi H, Iwase H, Shinohara M, Ando Y.
  • Journal Title: Br J Cancer 99 Pages: 655-662
  • Peer Reviewed
• [Journal Article] Synergistic induction of MUC5AC mucin by nontypeable Haemophilus influenzae and Streptococcus pneumoniae. (2008)
  • Author(s): Shen H, Yoshida H, Yan F, Li W, Xu F, Huang H, Jono H, Li JD.
  • Journal Title: Biochem Biophys Res Commun 365 Pages: 795-800
  • Peer Reviewed
• [Journal Article] Tumor suppressor cylindromatosis acts as a negative regulator for Streptococcus pneumoniae-induced NFAT signaling. (2008)
  • Author(s): Koga T(Jono H, 3^<rd>)
  • Journal Title: Journal of Biological Chemistry 283 Pages: 12546-12554
  • Peer Reviewed
• [Presentation] ヒト化抗IL-6受容体抗体を用いたグリオーマに対する抗腫瘍効果の検討 (2010)
  • Author(s): 城野博史、竹崎達也、神力悟、工藤真励奈、矢野茂敏、中村英夫、牧野敬史、秀拓一郎、牟田大助、植田光晴、倉津純一、安東由喜雄
  • Organizer: 第50回臨床化学会年会
  • Place of Presentation: 山梨県立県民文化ホール、山梨
  • Year and Date: 2010-09-23
• [Presentation] Effect of cyclodextrins on transthyretin amyloid formation. (2010)
  • Author(s): Jono H, Anno T, Misumi Y, Mori Y, Motoyama K, Ueda M,, Horibata Y, Shono M, Obayashi K, Arima H, Ando Y.
  • Organizer: XII International symposium on amyloidosis
  • Place of Presentation: Crown Plaza Rome, Rome, Italy.
• [Presentation] グリオーマの病態解析およびヒト化抗IL-6受容体抗体の抗腫瘍効果の検討 (2009)
  • Author(s): 城野博史、工藤真励奈、神力悟、矢野茂敏、中村英夫、牧野敬史、秀拓一郎、牟田大助、植田光晴、安東由喜雄、倉津純一
  • Organizer: 第49回日本臨床化学会年会
  • Place of Presentation: 長崎大学医学部、長崎
  • Year and Date: 2009-09-19
• [Presentation] シクロデキストリン誘導体を用いたTTR型アミロイドーシスのアミロイド線維形成抑制メカニズムの解析 (2009)
  • Author(s): 城野博史、安野貴幸、三隅洋平、本山敬一、植田光晴、大林光念、堀端洋子、有馬英俊、安東由喜雄
  • Organizer: 第56回日本臨床検査医学会学術集会
  • Place of Presentation: 札幌コンベンションセンター、札幌
  • Year and Date: 2009-08-28
• [Presentation] シクロデキストリン誘導体を用いた家族性アミロイドポリニューロパチー(FAP)の新規治療法の開発 (2009)
  • Author(s): 城野博史、安野貴幸、三隅洋平、大林光念、植田光晴、堀端洋子、有馬英俊、安東由喜雄
  • Organizer: 第27回日本神経治療学会総会
  • Place of Presentation: 熊本市民会館、熊本
  • Year and Date: 2009-06-11
• [Presentation] 分岐β-シクロデキストリンを用いたトランスサイレチンのアミロイド線維形成機構の解析 (2008)
  • Author(s): 城野博史、安野貴幸、本山敬一、三隅洋平、堀端洋子、植田光晴、有馬英俊、安東由喜雄
  • Organizer: 第55回日本臨床検査医学会総会
  • Place of Presentation: 名古屋国際会議場、名古屋
  • Year and Date: 2008-11-30
• [Presentation] Effect of Albumin on Transthyretin Amyloid Formation. (2008)
  • Author(s): Jono H, Saito S, Kugimiya T, Maruyama T, Misumi Y, Hoshii Y, Horibata Y, Ueda M, Otagiri M, Ando Y.
  • Organizer: VIIth International Symposium on Familial Amyloid Polyneuropathy
  • Place of Presentation: King's college London, London, UK.
  • Year and Date: 2008-09-03
• [Book] 脳機能を反映する血中バイオマーカーの現状と展望(医療と検査機器・試薬、ラボ・サービス、33) (2010)
  • Author(s): 城野博史、大林光念、安東由喜雄
• [Book] New Therapeutic Approaches for Familial Amyloidotic Polyneuropathy (FAP) Recent Advances in Transthyretin Evolution(Structure and Biological Functions) (2009)
  • Author(s): Ando Y, Nakamura M, Ueda M, Jono H.
  • Publisher: Springer, Chapter
• [Book] 季刊腎と骨代謝(β2-ミクログロブリンの分子修飾) (2009)
  • Author(s): 城野博史、安東由喜雄
  • Publisher: 臨床医学出版
• [Book] 臨床病理(トランスサイレチン型アミロイドーシスの病態解析と治療) (2008)
  • Author(s): 安東由喜雄、城野博史
  • Publisher: 克誠堂出版
• [Remarks] ホームページ等
  • URL: http://www2.kuh.kumamoto-u.ac.jp/diagnostic/index.htm