Functional analysis of CCN3, a novel growth inhibitor for vascular smooth muscle cells, and its application in the treatment of vascular diseases.

• Project/Area Number: 20591078
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Metabolomics
• Research Institution: Chiba University
• Principal Investigator: YOKOTE Koutaro Chiba University, 大学院・医学研究院, 教授 (20312944)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2010: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2009: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2008: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: CCN / 動脈硬化 / 平滑筋細胞 / 増殖 / 遊走 / 糖尿病 / CCN3 / 内膜肥厚 / Notch経路

Research Abstract

CCN3 belongs to CCN family, which constitutes multifunctional secreted proteins that act as matricellular regulators. CCN3 suppressed the rat smooth muscle cells (VSMC) migration as well as proliferation induced by fetal bovine serum. CCN3 knockout mice were created and the neointimal hyperplasia induced by photochemically-induced thrombosis, were investigated. Histopathological evaluation of the arteries 21 days after the endothelial injury revealed a 6-fold enhancement of neointimal thickening in the null mice compared with the wild-type. Our findings indicate the involvement of CCN3 in vascular homeostasis, especially upon injury, and the potential usefulness of this molecule in the modulation of atherosclerotic vascular disease.

Research Products

• [Journal Article] Primary lung cancer associated with Werner syndrome. (2011)
  • Author(s): Ohnishi, S, et al.
  • Journal Title: Geriatr Gerontol Int Volume: 10 Pages: 319-323
  • Peer Reviewed
• [Journal Article] Primary lung cancer associated with Werner syndrome. (2010)
  • Author(s): Ohnishi, S., Fujimoto, M., Oide, T., Nakatani, Y., Tsurutani, Y., Koshizaka, M., Mezawa, M., Ishikawa, T., Takemoto, M., Yokote, K.
  • Journal Title: Geriatr Gerontol Int. 10(4) Pages: 319-323
  • NAID: 10027755431
  • Peer Reviewed
• [Journal Article] Phosphate-activated glutaminase (GLS2), a p53-inducible regulator of glutamine metabolism and reactive oxygen species. (2010)
  • Author(s): Suzuki S, Tanaka T, Poyurovsky MV, Nagano H, Mayama T, Ohkubo S, Lokshin M, Hosokawa H, Nakayama T, Suzuki Y, Sugano S, Sato E, Nagao T, Yokote K, Tatsuno I, Prives C.
  • Journal Title: Proc Natl Acad Sci USA 107 Pages: 7461-7466
  • Peer Reviewed
• [Journal Article] Mexiletine suppresses nodal persistent sodium currents in sensory axons of patients with neuropathic pain. (2010)
  • Author(s): Isose S, Misawa S, Sakurai K, Kanai K, Shibuya K, Sekiguchi Y, Nasu S, Noto Y, Fujimaki Y, Yokote K, Kuwabara S.
  • Journal Title: Clin Neurophysiol. 121 Pages: 719-724
  • Peer Reviewed
• [Journal Article] Hypoglycemia due to ectopic secretion of insulin-like growth factor-I in a patient with an isolated sarcoidosis of the spleen. (2010)
  • Author(s): Ogiwara Y, Mori S, Iwama M, Sawabe M, Takemoto M, Kanazawa N, Furuta K, Fukuda I, Kondo Y, Kimbara Y, Tamura Y, Chiba Y, Araki A, Yokote K, Maruyama N, Ito H.
  • Journal Title: Endocr J. 57 Pages: 325-330
  • NAID: 10029584375
  • Peer Reviewed
• [Journal Article] Effects of Pitavastatin (LIVALO Tablet) on the Estimated Glomerular Filtration Rate (eGFR) in Hypercholesterolemic Patients with Chronic Kidney Disease. (2010)
  • Author(s): Kimura K, Shimano H, Yokote K, Urashima M, Teramoto T.
  • Journal Title: J Atheroscler Thromb. 17 Pages: 601-606
  • Peer Reviewed
• [Journal Article] CCN3 Inhibits Neointimal Hyperplasia Through Modulation of Smooth Muscle Cell Growth and Migration. (2010)
  • Author(s): Shimoyama,T., Hiraoka, S., Takemoto, M., Koshizaka, M., Tokuyama, H., Tokuyama, T., Watanabe, A., Fujimoto, M., Kawamura, H., Sato, S., Tsurutani, Y., Saito, Y., Perbal, B., Koseki, H., Yokote, K.
  • Journal Title: Arterioscler Thromb Vasc Biol.30 Pages: 675-682
  • Peer Reviewed
• [Journal Article] Effects of Pitavastatin (LIVALO Tablet) on the Estimated Glomerular Filtration Rate (eGFR) in Hypercholesterolemic Patients with Chronic Kidney Disease. (2010)
  • Author(s): Kimura, K, et al.
  • Journal Title: J Atheroscler Thromb Volume: 17 Pages: 601-609
  • Peer Reviewed
• [Journal Article] CCN3 Inhibits Neointimal Hyperplasia Through Modulation of Smooth Muscle Cell Growth and Mieration. (2010)
  • Author(s): Shimoyama, T, et al.
  • Journal Title: Arterioscler Thromb Vasc Biol Volume: 30 Pages: 675-682
  • Peer Reviewed
• [Journal Article] CCN3 inhibits neointimal hyperplasia through modulation of smooth muscle cell growth and migration. (2009)
  • Author(s): Shimoyama T
  • Journal Title: Arterioscler Thromb Vasc Biol. 30 Pages: 675-682
  • Peer Reviewed
• [Journal Article] Perturbation of Hepatic TGF-β Signaling by HepatitisB Virus X Protein in Chronic Hepatitis. (2009)
  • Author(s): Murata, M
  • Journal Title: Hepatology 49 Pages: 1203-1217
  • Peer Reviewed
• [Journal Article] Low HDL cholesterol is associated with the risk of stroke in elderly diabetic individuals : changes in the risk for atherosclerotic diseases at various ages. (2009)
  • Author(s): Hayashi T
  • Journal Title: Diabetes Care 32 Pages: 1221-1223
  • Peer Reviewed
• [Journal Article] Effects of Pitavastatin(LIVALO Tablet)on High Density Lipoprotein Cholesterol(HDL-C)in Hypercholesterolemia : Sub-analysis of LIVALO Effectiveness and Safety(LIVES)Study (2009)
  • Author(s): Teramoto T
  • Journal Title: J Atheroscler Thromb. 49 Pages: 1203-1217
  • Peer Reviewed
• [Journal Article] Clinical outcome and mechanism of soft tissue calcification in Werner syndrome. (2008)
  • Author(s): Honjo s. et al
  • Journal Title: Rejuvenation Res. 11 Pages: 809-819
  • Peer Reviewed
• [Journal Article] Multicenter collaborative randomized parallel group comparative study of pitavastatin and atorvastatin in Japanese hypercholesterolemic patients-Collaborative study on Hypercholesterolemia drug Intervention and their Benefits for Atherosclerosis prevention (2008)
  • Author(s): Yokote K et al.
  • Journal Title: Atherosclerosis 201 Pages: 345-352
  • Peer Reviewed
• [Journal Article] Halofuginone prevents extracellular matrix deposition in diabetic nephropathy. (2008)
  • Author(s): Sato S et al.
  • Journal Title: Biochem Biophys Res Commun 379 Pages: 411-416
  • Peer Reviewed
• [Journal Article] Hypoglycemia due to Ectopic Secretion of Insulin-Like Growth Factor-I in a Patient with an Isolated Sarcoidosis of the Spleen.
  • Author(s): Ogawa Y
  • Journal Title: Endocrine Journal (In press)
  • Peer Reviewed
• [Journal Article] Influence of statins on glucose tolerance in patients with type 2 diabetes mellitus : a subanalysis of Collaborative study on Hypercholesterolemia drug Intervention and their Benefits for Atherosclerosis prevention.
  • Author(s): Yokote, K
  • Journal Title: J Atheroscler Thromb. (In press)
  • Peer Reviewed
• [Presentation] Inhibitory effect of CCN3 on arterial neointimal hyperplasia though modulation of smooth muscle cell growth migration. (2010)
  • Author(s): Yokote., K
  • Organizer: 6th INTERNATIONAL CCN WORKSHOP
  • Place of Presentation: Northern Ireland
  • Year and Date: 2010-10-20
• [Presentation] 新たな抗肥満薬とその展望 (2010)
  • Author(s): 横手幸太郎
  • Organizer: 第31回日本肥満学会
  • Place of Presentation: 群馬
  • Year and Date: 2010-10-02
• [Presentation] 動脈硬化予防の現状と展望 (2010)
  • Author(s): 横手幸太郎
  • Organizer: 第31回日本肥満学会
  • Place of Presentation: 群馬
  • Year and Date: 2010-10-01
• [Presentation] 新しい診断基準における合併症の考え方 (2010)
  • Author(s): 横手幸太郎
  • Organizer: 第31回日本肥満学会
  • Place of Presentation: 群馬
  • Year and Date: 2010-10-01
• [Presentation] 新しい診断基準における合併症の考え方 (2010)
  • Author(s): 横手幸太郎
  • Organizer: 第31回日本肥満学会
  • Place of Presentation: 前橋市
  • Year and Date: 2010-10-01
• [Presentation] 日本におけるスタチン治療のエビデンス (2010)
  • Author(s): 横手幸太郎
  • Organizer: 第42回日本動脈硬化学会総会・学術集会
  • Place of Presentation: 岐阜
  • Year and Date: 2010-07-16
• [Presentation] 臼本におけるスタチン治療のエビデンス (2010)
  • Author(s): 横手幸太郎
  • Organizer: 第42回日本動脈硬化学会総会・学術集会
  • Place of Presentation: 岐阜市
  • Year and Date: 2010-07-16
• [Presentation] Trends in guidelines overseas. Special symposium : Update for JAS guideline on management of Atherosclerosis. (2010)
  • Author(s): 横手幸太郎
  • Organizer: The 42nd Annual scientific Meeting of the Japan Atherosclerosis Society.
  • Place of Presentation: Gifu
  • Year and Date: 2010-07-15
• [Presentation] ウエルナー症候群の病態把握、診療指針作成と新規治療法の開発を目的とした全国研究 (2010)
  • Author(s): 石川崇弘、竹本稔、藤本昌紀、葛谷雅文、森聖二郎、横手幸太郎
  • Organizer: 第52回日本老年病医学会学術集会
  • Place of Presentation: 神戸
  • Year and Date: 2010-06-25
• [Presentation] 高脂血症 (2010)
  • Author(s): 横手幸太郎
  • Organizer: 第52回日本老年医学会学術集会
  • Place of Presentation: 神戸
  • Year and Date: 2010-06-24
• [Presentation] 質異常から見たCKDへのアプローチ (2010)
  • Author(s): 横手幸太郎
  • Organizer: 第53回日本腎臓学会学術総会ランチョンセミナー6
  • Place of Presentation: 神戸
  • Year and Date: 2010-06-16
• [Presentation] 早老症から学ぶ血管のアンチエイジング (2010)
  • Author(s): 横手幸太郎
  • Organizer: 第10回日本抗加齢医学会総会
  • Place of Presentation: 京都
  • Year and Date: 2010-06-13
• [Presentation] WRN遺伝子に複合型ヘテロ接合体変異を同定したウェルナー症候群の一例 (2010)
  • Author(s): 田守義和、高橋哲也、中島進介、西本祐希、大野恭太、竹本稔、横手幸太郎、喜多哲也
  • Organizer: 第191回日本内科学会近畿地方会
  • Place of Presentation: 京都
  • Year and Date: 2010-06-12
• [Presentation] 我が国における脂質関連大規模臨床試験 (2010)
  • Author(s): 横手幸太郎
  • Organizer: 第53回日本糖尿病学会年次学術集会
  • Place of Presentation: 岡山
  • Year and Date: 2010-05-28
• [Presentation] 糖尿病・IGTにおけるスタチンの役割:臨床的立場から (2010)
  • Author(s): 横手幸太郎
  • Organizer: 第53回日本糖尿病学会年次学術集会、ランチョンセミナー25
  • Place of Presentation: 岡山
  • Year and Date: 2010-05-28
• [Presentation] Twist-1 : A new negative-feedback regulator of peroxisome proliferator-activated receptor-gamma co-activator-1. (2010)
  • Author(s): Fujimoto, M., Yokote, K.
  • Organizer: The 14th International Congress of Endocrinology (ICE2010).
  • Place of Presentation: Kyoto.
  • Year and Date: 2010-03-29
• [Presentation] 透析中に早朝低血糖を繰り返し、インスリノーマと診断された1例。 (2010)
  • Author(s): 樋口誠一郎, 他
  • Organizer: 第47回日本糖尿病学会 関東甲信越地方会
  • Place of Presentation: 大宮
  • Year and Date: 2010-01-30
• [Presentation] 日常診療の中でTG・HDLをどう考えどう治療するか? (2010)
  • Author(s): 横手幸太郎
  • Organizer: 第44回日本成人病(生活習慣病)学術集会
  • Place of Presentation: 東京
  • Year and Date: 2010-01-09
• [Presentation] 早老症から学ぶ血管のアンチエイジング (2010)
  • Author(s): 横手幸太郎
  • Organizer: 第10回日本抗加齢医学会総会
  • Place of Presentation: 京都市
• [Presentation] 脂質異常から見たCKDへのアプローチ (2010)
  • Author(s): 横手幸太郎
  • Organizer: 第53回日本腎臓学会学術総会ランチョンセミナー6
  • Place of Presentation: 神戸市
• [Presentation] 高脂血症 (2010)
  • Author(s): 横手幸太郎
  • Organizer: 第52回日本老年医学会学術集会
  • Place of Presentation: 神戸市
• [Presentation] 動脈硬化予防の現状と展望 (2010)
  • Author(s): 横手幸太郎
  • Organizer: 第31回日本肥満学会
  • Place of Presentation: 前橋市
• [Presentation] 体質と高脂血症。 (2009)
  • Author(s): 横手幸太郎
  • Organizer: 日本体質医学会総会
  • Place of Presentation: 東京
  • Year and Date: 2009-07-25
• [Presentation] 動脈硬化形成におけるCCNファミリー分子NOVの役割に関する検討 (2008)
  • Author(s): 下山立志、他
  • Organizer: 第40回日本動脈硬化学会
  • Place of Presentation: エポカルつくば(つくば市)
  • Year and Date: 2008-07-11
• [Book] 今日の診断指針、6(Werner症候群) (2010)
  • Author(s): 横手幸太郎
  • Publisher: 医学書院
• [Book] NHKきょうの健康大百科 (2010)
  • Author(s): 横手幸太郎
  • Publisher: NHK出版
• [Book] 日経メディカル (2010)
  • Author(s): 横手幸太郎
  • Publisher: 日経BP
• [Book] The Lipid (2010)
  • Author(s): 横手幸太郎
  • Publisher: メディカルレビュー社
• [Book] ザィ・ピア51, 動脈硬化をめぐって予防と治療の新し喉開 (2010)
  • Author(s): 横手幸太郎
  • Publisher: FUJIREBIO INC
• [Book] Geriatric Medicine (2010)
  • Author(s): 横手幸太郎
  • Publisher: 老年医学
• [Book] 心血管リメクを防ぐ!高血圧診療ガイド. (2010)
  • Author(s): 王子剛, 他
  • Publisher: 南山堂
• [Book] 糖尿病・高血圧合併例の脂質異常コントロール (2010)
  • Author(s): 滝口朋子, 他
  • Publisher: 日本医事新報
• [Book] 細胞The CELL (2010)
  • Author(s): 横手幸太郎
  • Publisher: ニューサイエンス社
• [Book] 動脈硬化性疾患予防のための脂質異常症治療ガイド2008年版 (2008)
  • Author(s): 日本動脈硬化学会編
  • Total Pages: 105
  • Publisher: 協和企画(東京)