Investigation of roles of resistin like molecule beta in pathogenesis of atherosclerosis

• Project/Area Number: 19790644
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Metabolomics
• Research Institution: The Institute for Adult Diseases, Asahi Life Foundation
• Principal Investigator: KUSHIYAMA Akifumi The Institute for Adult Diseases, Asahi Life Foundation, その他部局等, 准教授 (30435820)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥3,530,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥330,000); Fiscal Year 2008: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2007: ¥2,100,000 (Direct Cost: ¥2,100,000)
• Keywords: 動脈硬化症 / 血管内皮機能 / 血管新生 / RELMβ / マクロファージ

Research Abstract

レジスチン様分子β(RELMβ)は血管内皮細胞に対し増殖活性・遊走能亢進活性を示して血管新生(弱く破れやすい血管が増え、動脈硬化巣が破れすくなり心筋梗塞や脳梗塞を生じやすい)を生じ、一方で内皮機能障害(血管をリラックスさせる反応が低下すること)を来した。また実際に生体の中でもRELMβの濃度が上昇すると動脈硬化が進行することが示された。国民的・世界的な疾病である心筋梗塞・脳梗塞などの動脈硬化性疾患にレジスチン様分子が関与する可能性が示された。

Research Products

• [Journal Article] Long-term forskolin stimulation induces AMPK activation and thereby enhances tight junction formation in human placental trophoblast BeWo cells. (2008)
  • Author(s): Egawa M, Kamata H, Kushiyama A, Sakoda H, Fujishiro M, Horike N, Yoneda M, Nakatsu Y, Ying G, Jun Z, Tsuchiya Y, Takata K, Kurihara H, Asano T
  • Journal Title: Placenta 29(12) Pages: 1003-8
• [Journal Article] AMP-activated protein kinase activation increases phosphorylation of glycogen synthase kinase 3beta and thereby reduces cAMP-responsive element transcriptional activity and phosphoenolpyruvate carboxykinase C gene expression in the liver. (2008)
  • Author(s): Horike N, Sakoda H, Kushiyama A, Ono H, Fujishiro M, Kamata H, Nishiyama K, Uchijima Y, Kurihara Y, Kurihara H, Asano T
  • Journal Title: J Biol Chem. 283(49) Pages: 33902-10
• [Journal Article] Hepatic overexpression of a dominant negative form of raptor enhances Akt phosphorylation and restores insulin sensitivity in K/KAy mice. (2008)
  • Author(s): Koketsu Y, Sakoda H, Fujishiro M, Kushiyama A, Fukushima Y, Ono H, Anai M, Kikuchi T, Fukuda T, Kamata H, Horike N, Uchijima Y, Kurihara H, Asano T
  • Journal Title: Am J Physiol Endocrinol Metab 294(4)
• [Journal Article] Regulation of gut-derived resistin-like molecule beta expression by nutrients. (2008)
  • Author(s): Fujio J, Kushiyama A, Sakoda H, Fujishiro M, Ogihara T, Fukushima Y, Anai M, Horike N, Kamata H, Uchijima Y, Kurihara H, Asano T
  • Journal Title: Diabetes Res Clin Pract 79(1) Pages: 2-10
• [Journal Article] Long-term forskolin stimulation induces AMPK activation and thereby enhances tight junction formation in human placental trophoblast BeWo cells. (2008)
  • Author(s): Egawa M, 櫛山暁史, 他
  • Journal Title: Placenta 29 Pages: 1003-8
  • Peer Reviewed
• [Journal Article] AMP-activated protein kinase activation increases phosphorylation of glycogen synthase kinase 3beta and thereby reduces cAMP-responsive element transcriptionaI activity and phosphoenolpyruvate carboxykinase C gene expression in the liver. (2008)
  • Author(s): Horike N, 櫛山暁史, 他
  • Journal Title: J Biol Chem 283 Pages: 33902-10
  • Peer Reviewed
• [Journal Article] Hepatic overexpression of a dominant negative form of raptor enhances Akt phosphorylation and restores insulin sensitivity in K/KAy mice. (2008)
  • Author(s): Koketsu N, 櫛山暁史, 他
  • Journal Title: Am J Physiol Endocrinol Metab. 294
  • Peer Reviewed
• [Journal Article] Regulation of gut-derived resistin-like molecule beta expression by nutrients (2008)
  • Author(s): Fujio J, 櫛山 暁史, 他
  • Journal Title: Diabetes Research and Clinical Practice 79 Pages: 2-10
  • Peer Reviewed
• [Journal Article] Role of phosphatidylinositol 3-kinase activation on insulin action and its alteration in diabetic conditions. (2007)
  • Author(s): Asano T, Fujishiro M, Kushiyama A, Nakatsu Y, Yoneda M, Kamata H, Sakoda H
  • Journal Title: Biol Pharm Bull 30(9) Pages: 1610-6
  • NAID: 110006380237
• [Journal Article] Carboxy-terminal modulator protein induces Akt phosphorylation and activation, thereby enhancing antiapoptotic, glycogen synthetic, and glucose uptake pathways. (2007)
  • Author(s): Ono H, Sakoda H, Fujishiro M, Anai M, Kushiyama A, Fukushima Y, Katagiri H, Ogihara T, Oka Y, Kamata H, Horike N, Uchijima Y, Kurihara H, Asano T
  • Journal Title: Am J Physiol Cell Physiol 293(5)
• [Journal Article] Physiological significance of resistin and resistin-like molecules in the inflammatory process and insulin resistance. (2006)
  • Author(s): Asano T, Sakoda H, Fujishiro M, Anai M, Kushiyama A, Horike N, Kamata H, Ogihara T, Kurihara H, Uchijima Y
  • Journal Title: Curr Diabetes Rev. 2(4) Pages: 449-54
• [Presentation] Functionally distinct roles of each member of the resistin family in insulin resistance and atherosclerosis (2008)
  • Author(s): 櫛山 暁史, 他
  • Organizer: 68^<th> ADA scientific session
  • Place of Presentation: San Francisco, USA
  • Year and Date: 2008-06-08
• [Presentation] インスリン抵抗性を誘導するレジスチンファミリー(resistin/RELMβ)は各々異なった機序で動脈硬化に関与する (2008)
  • Author(s): 櫛山 暁史, 他
  • Organizer: 第51回日本糖尿病学会学術総会
  • Place of Presentation: Tokyo
  • Year and Date: 2008-05-24
• [Presentation] Functionally distinct roles of each member of the resistin family in insulin resistance and atherosclerosis (2008)
  • Author(s): A. Kushiyama, H. Sakoda, M. Fujishiro, H. Ohno, M. Yoneda, Y. Nakatsu, H. Kamata, M. Kikuchi, T. Asano
  • Organizer: 68th American Diabetes Association Scientific Sessions
  • Place of Presentation: San Francisco, USA
• [Presentation] インスリン抵抗性を誘導するレジスチンファミリー(resistin/RELMβ)は各々異なった機序で動脈硬化に関与する (2008)
  • Author(s): 櫛山暁史, 浅野知一郎, 迫田秀之, 藤城緑, 纐纈優子, 福田武俊, 佃克則, 大西由希子, Amelia, 犬飼浩一, 菊池方利
  • Organizer: 第51回日本糖尿病学会年次学術集会
  • Place of Presentation: 東京都
• [Presentation] Resistin-like molecule(RELM)βは内皮機能障害及び炎症反応を介して動脈硬化に関与する (2007)
  • Author(s): 櫛山暁史, 浅野知一郎, 迫田秀之, 藤城緑, 纐纈優子, 穴井元暢, 油谷浩幸, 栗原裕基, 菊池方利
  • Organizer: BMB2007
  • Place of Presentation: 神奈川県
  • Year and Date: 2007-12-13
• [Presentation] Resistin like molecule beta induces atherosclerosis via directly impairing vascular endothelial function and priming inflammation as a mediator of immune-response (2007)
  • Author(s): 櫛山 暁史, 他
  • Organizer: BMB2007
  • Place of Presentation: Yokohama
  • Year and Date: 2007-12-13
• [Presentation] Increased RELMβ expression in saturated fatty acid-treated colonic cells: possible involvement of toll-like receptors (2007)
  • Author(s): A. Y. I VIANA, 櫛山 暁史, 他
  • Organizer: 13th international congress of immunology
  • Place of Presentation: Rio de Janeiro
  • Year and Date: 2007-08-21
• [Presentation] 腸管由来RELM(resistin like molecules)βは動脈硬化・メタボリック症候群に関与する (2007)
  • Author(s): 櫛山 暁史, 他
  • Organizer: 第50回日本糖尿病学会学術総会
  • Place of Presentation: Sendai
  • Year and Date: 2007-05-26
• [Remarks]
  • URL: http://www.asahi-life.or.jp/laboratory/biomolecular.html
• [Remarks]
  • URL: http://www.asahi-life.or.jp/laboratory/biomolecular.html
• [Remarks]
  • URL: http://www.asahi-life.or.jp/laboratory/theses.html
• [Patent(Industrial Property Rights)] 大腸癌、動脈硬化症、又はメタボリックシンドロームの検出方法 (2007)
  • Inventor(s): 櫛山暁史・浅野知一郎
  • Industrial Property Rights Holder: 櫛山暁史・浅野知一郎
  • Filing Date: 2007-12-12
• [Patent(Industrial Property Rights)] 大腸癌、動脈硬化症、又はメタボリックシンドロームの検出方法 (2007)
  • Inventor(s): 浅野 知一郎、櫛山 暁史
  • Industrial Property Rights Holder: 浅野 知一郎、櫛山 暁史
  • Filing Date: 2007-12-12