Genesis and physiologic significance of secretory RAGE-a new vasoprotective factor

2010 Fiscal Year Final Research Report

• Project/Area Number: 19390085
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Pathological medical chemistry
• Research Institution: Kanazawa University
• Principal Investigator: YAMAMOTO Hiroshi Kanazawa University, 医学系, 教授 (00115198)
• Co-Investigator(Kenkyū-buntansha): WATANABE Takuo 金沢大学, 医学系, 准教授 (40303268)
• Co-Investigator(Renkei-kenkyūsha): YAMAMOTO Yasuhiko 金沢大学, 医学系, 講師 (20313637) ; MUNESUE Seiichi 金沢大学, 医学系, 助教 (10399040)
• Project Period (FY): 2007 – 2010
• Keywords: RAGE / 分泌型バリアント / RNAスプライシング / 遺伝子改変動物 / アルツハイマー病 / LPS誘発ショック / アポトーシス

Research Abstract

First, we identified cis-acting regulatory elements and a putative trans-acting factor that may participate in the production of secretory RAGE. Second, we created a secretory RAGE-overexpressing transgenic mouse model, and demonstrated with it that RAGE accounts for the transition of amyloid・into the brain. Further, we also found that RAGE is involved in lipopolysaccharide-induced inflammation and in phosphatidyl serine-mediated apoptosis.

Research Products

• [Journal Article] Endogenous Secretory Receptor for AGE Inhibits Amyloid-β_<1-42> Uptake into Mouse Brain (2011)
  • Author(s): Sugihara T, Munesue S, Yamamoto Y, Sakaurai S, Akhter N, Kitamura Y, Shiba k, Watanabe T, Yonekura H, Hayashi Y, Hamada J, Yamamoto H
  • Journal Title: (投稿中)
  • Peer Reviewed
• [Journal Article] Inhibition of allergic bronchial asthma by thrombomodulin is mediated by dendritic cells. (2011)
  • Author(s): Takagi T, Taguchi O, Toda M, Ruiz DB, Bernabe PG, D'Alessandro-Gabazza CN, Miyake Y, Kobayashi T, Aoki S, Chiba F, Yano Y, Conway EM, Munesue S, Yamamoto Y, Yamamoto H, Suzuki K, Takei Y, Morser Y, ?Gabazza EC
  • Journal Title: Am.J.Respir.Crit.Care Med. 183 Pages: 31-42
  • Peer Reviewed
• [Journal Article] The effects of receptor for advanced glycation end products (RAGE) on bone metabolism under physiological and diabetic condition. (2010)
  • Author(s): Hamada Y, Kitazawa S, Kitazawa R, Kono K, Goto S, Komaba H, Fujii H, Yamamoto Y, Yamamoto H, Usami M, Fukagawa M
  • Journal Title: Endocrine in press
  • Peer Reviewed
• [Journal Article] Glycation of a food allergen by the Maillard reaction enhances its T-cell immunogenicity : Role of macrophage scavenger receptor class A type I and II. (2010)
  • Author(s): IIchmann A, Burgdorf S, Scheurer S, Waibler Z, Nagai R, Wellner A, Yamamoto Y, Yamamoto H, Henle T, Kurts C, Kalinke U, Vieths S, Toda M
  • Journal Title: J.Allergy Clin.Immunol. 125 Pages: 175-183
  • Peer Reviewed
• [Journal Article] High-mobility group box 1 is involved in the initial events of early loss of transplanted islets in mice. (2010)
  • Author(s): Matsuoka N, Itch T, Watarai H, Sekine-Kondo E, Nagata N, Okamoto K, Mera T, Yamamoto H, Yamada S, Maruyama I, Taniguchi M, Yasunami Y
  • Journal Title: J.Clin.Invest. 120 Pages: 735-743
  • Peer Reviewed
• [Journal Article] Receptor for advanced glycation end-products (RAGE) regulation of adiposity and adiponectin is associated with atherogenesis in ape E-deficient mouse. (2010)
  • Author(s): Ueno H, Koyama H, Shoji T, Kurato M, Fukumoto S, Tanaka S, Otsuka Y, Mima Y, Morioka T, Mori K, Shioi A, Yamamoto H, Inaba M, Nishizawa Y
  • Journal Title: Atherosclerosis 211 Pages: 431-436
  • Peer Reviewed
• [Journal Article] Cooper ME, Forbes JM : Recepter for AGEs(RAGE) blockade may exert its renoprotective effects in patients with diabetic nephropathy via induction of the angiotensin type 2 (AT2) receptor. (2010)
  • Author(s): Sourris KC, Morley AL, Koitka A, Samuel P, Coughlan MT, Penfold SA, Tomas MC, Bierhaus A, Nawroth PP, Yamamoto H, Allen TJ, Walther T, Hussain T
  • Journal Title: Diabetologia 53 Pages: 2442-2451
  • Peer Reviewed
• [Journal Article] Blockade of endothelial-mesenchymal-transition by a Smad3 inhibitor delays the early development of streptozotocin-induced diabetic nephropathy. (2010)
  • Author(s): Li J, Qu X, Yao J, Caruana G, Ricardo SD, Yamamoto Y, Yamamoto H, Bertram JF
  • Journal Title: Diabetes 59 Pages: 2612-2624
  • Peer Reviewed
• [Journal Article] Regulation of alternative splicing of the receptor for advanced glycation endproducts (RAGE) through G-rich cis-elements and heterogenous nuclear ribonucleoprotein (hnRNP) (2010)
  • Author(s): Ohe K, Watanabe T, Harada S, Munesue S, Yamamoto Y, Yonekura H, Yamamoto H
  • Journal Title: H.J.Biochem. 147 Pages: 651-659
  • Peer Reviewed
• [Journal Article] Deletion of RAGE causes hyperactivity and increased sensitivity to auditory stimuli in mice. (2009)
  • Author(s): Sakatani S, Yamada K, Homma C, Munesue S, Yamamoto Y, Yamamoto H, Hirase H
  • Journal Title: PLoS ONE 4(12:e8309) Pages: 1-7
  • Peer Reviewed
• [Journal Article] RAGE mediates oxidized LDL-induced pro-inflammatory effects and atherosclerosis in non-diabetic LDL receptor-deficient mice. (2009)
  • Author(s): Sun L, Ishida T, Yasuda T, Kojima Y, Honjo T, Yamamoto Y, Yamamoto H, Ishibashi S, Hirata K, Hayashi Y
  • Journal Title: Cardiovascular Research 82 Pages: 371-381
  • Peer Reviewed
• [Journal Article] Neural activity dependent release of S100B from astrocytes enhances kainate-induced gamma oscillations in vivo. (2008)
  • Author(s): Sakatani S, Seto-Ohshima A, Shinohara Y, Yamamoto Y, Yamamoto H, Ttohara S, Hirase H
  • Journal Title: J.Neuroscience 28(43) Pages: 10928-10936
  • Peer Reviewed
• [Journal Article] Angiotensin upregulates RAGE expression on podocytes : Role of AT2 receptors. (2008)
  • Author(s): Ruster C, Bondeva T, Franke S, Tanaka N, Yamamoto H, WolfG
  • Journal Title: Am.J.Nephrol. 29 Pages: 538-550
  • Peer Reviewed
• [Journal Article] Solution structure of the variable-type domain of the receptor for advanced glycation end products : New insight into AGE-RAGE interaction. (2008)
  • Author(s): Matsumoto S, Yoshida T, Murata H, Harada S, Fujita N, Nakamura S, Yamamoto Y, Watanabe T, Yonekura H, Yamamoto H, Ohkubo T, Kobayashi Y
  • Journal Title: Biochemistry 47(47) Pages: 12299-12311
  • Peer Reviewed
• [Journal Article] Reduced expression of endogenous secretory receptor for advanced glycation endproducts in hippocampal neurons of Alzheimer's disease brains. (2007)
  • Author(s): Nozaki I, Watanabe T, Kawaguchi M, Akatsu H, Tsuneyama K, Yamamoto Y, Ohe K, Yonekura H, Yamada M, Yamamoto H
  • Journal Title: Arch.Histol.Cytol. 70 Pages: 279-290
  • Peer Reviewed
• [Journal Article] RAGE in diabetic nephropathy. (2007)
  • Author(s): Yamamoto H, Watanabe T, Yamamoto Y, Yonekura H, Munesue S, Harashima A, Ohe K, Hossain S, Saito H, Murakami N
  • Journal Title: Curr.Mol.Med. 7 Pages: 752-757
  • Peer Reviewed
• [Journal Article] RAGE and soluble RAGE : potential therapeutic targets for cardiovascular diseases. (2007)
  • Author(s): Koyama H, Yamamoto H Nishizawa Y
  • Journal Title: Mel.Med. 13(11-12) Pages: 625-635
  • Peer Reviewed
• [Journal Article] The role of the receptor for advanced glycation end-products in lung fibrosis. (2007)
  • Author(s): He M, Kobe H, Tshizawa K, Hegab AE, Yamamoto Y, Yamamoto H, Yamaya M
  • Journal Title: Am.J.Physiol.Lung Cull.Met.Physiol. 293(6) Pages: L1427-36
  • Peer Reviewed
• [Journal Article] De-N-glycosylation or G82S mutation of RAGE sensitizes its interaction with advanced glycation endproducts. (2007)
  • Author(s): Osawa M, Yamamoto Y, Munesue S, Murakami N, Sakurai S, Watanabe T, Yonekura H, Uchigata Y, Iwamoto Y, Yamamoto H
  • Journal Title: Biochim.Biophys.Acta 1770(10) Pages: 1468-1474
  • Peer Reviewed
• [Journal Article] Assaying soluble forms of receptor for advanced glycation endproducts. (2007)
  • Author(s): Yamamoto Y, Miura J, Matsuki H., Tamei H., Obata K., Sakurai S, Watanabe T, Uchigata Y, Iwamoto Y, Koyama H, Yamamoto H.
  • Journal Title: Arterioscler.Thromb.Vase.Biol.s 27 Pages: e33-e34
  • Peer Reviewed
• [Journal Article] Short-chain aldehyde-derived ligands for RAGE and their actions on endothelial cells. (2007)
  • Author(s): Yamamoto Y, Yonekura H, Watanabe T, Sakurai S, Li H, Harashima A, Myint KM, Osawa M, Takeuchi A, Takeuchi M, Yamamoto H
  • Journal Title: Diabetes Res.Clin.Pract. 77S Pages: S30-S40
  • Peer Reviewed
• [Journal Article] Endogenous secretory receptor for advanced glycation end-producs as a novel prognostic marker in chondrosarcoma. (2007)
  • Author(s): Takeuchi A, Yamamoto Y, Tsuneyama K, Cheng C, Yonekura H, Watanabe T, Shimizu K, Tomita K, Yamamoto H, Tsuchiya H.
  • Journal Title: Cancer 109 Pages: 2532-2540
  • Peer Reviewed
• [Journal Article] Inhibition of diabetic leukostasis and blood-retinal barrier breakdown with a soluble form of a receptor for advanced glycation end products. (2007)
  • Author(s): Kaji Y, Usui T, Ishida S, Yamashiro K, Moore CB Tara, Moore J, Yamamoto Y, Yamamoto H, Adamis AP
  • Journal Title: Investigative Ophthalmology and Visual Science 48 Pages: 858-856
  • Peer Reviewed
• [Journal Article] Endogenous secretory receptor for advanced glycation end products in non-small cell lung carcinoma. (2007)
  • Author(s): Kobayashi S, Kubo H, Suzuki R, Ishizawa K, Yamada M, He M, Yamamoto Y, Yamamoto H, Sasano H, Sasaki H, Suzuki S
  • Journal Title: Am.J.Respir.Crit.Care Med. 175 Pages: 184-189
  • Peer Reviewed
• [Journal Article] Low circulating endogenous secretory receptor for AGEs (esRAGE) predicts cardiovascular mortality in patients with end-stage renal disease. (2007)
  • Author(s): Koyama H, Shoji T, Fukumoto S, Shinohara K, Shoji T, Emote M, Mori K, Tahara H, Ishimura E, Kakiya R, Tabata T, Yamamoto H, Nishizawa Y
  • Journal Title: Arterioseler.Thromb.Vase.Biol. 27 Pages: 147-153
  • Peer Reviewed
• [Journal Article] Endogenous secretory receptor for advanced glycation endproducts levels are correlated with serum pentosidine and CML in patients with type 1 diabetes. (2007)
  • Author(s): Miura J, Yamamoto Y, Osawa M, Watanabe T, Yonekura H, Uchigata Y, Yamamoto H, Iwamoto Y
  • Journal Title: Arterioscler.Thromb.Vasc.Biol. 27 Pages: 253-254
  • Peer Reviewed
• [Presentation] cAMP Exerts Anti-Inflammatory Effects by Controling RAGE Isoform Biogenesis. (2010)
  • Author(s): Sob Motoyoshi, Yasuhiko Yamamoto, Seiichi Munesue, Takuo Watanabe, Hiroshi Yamamoto
  • Organizer: 70^<th> American Diabetes Association Scientific Sessions
  • Place of Presentation: Orland USA(会場:オーランドコンベンションセンター)
  • Year and Date: 20100625-20100629
• [Presentation] Enemies and friends within in the pathogenesis and prevention of diabetic vascular complications. (2010)
  • Author(s): Yamamoto H, Watanabe T, Yamamoto Y, Yonekura H, Munesue S Ohe K, Sugihara T^1 Saito H, Motoyoshi S, Han D, Win MTT, Abou-Zed TK, Ohara T
  • Organizer: 4^<th> international HMGBI Symposium - Signals of Tissue Damage.
  • Place of Presentation: Helsinki, Finland(会場:ヘルシンキ大学)
  • Year and Date: 20100620-20100623
• [Presentation] Mechansims for the development of diabetic angiopathy and its prevention : Enemies and friends within. (2009)
  • Author(s): Yamamoto H, Watanabe T, Yamamoto Y, Yonekura H, Munesue S, Ooe K, Sugihara T, Saito H, Motoyoshi S, Han D
  • Organizer: 2^<nd> International Symposium on Adipobiology and Adipopharmacolgy
  • Place of Presentation: Varna, Bulgaria(会場:The Festival and Congress Center)
  • Year and Date: 20091023-20091025
• [Book] 糖化による疾患と抗糖化食品・素材序編-2、1編-5、1編-12 (2010)
  • Author(s): 山本博、久保田浩之、杉原崇大、山本靖彦
  • Publisher: (株)シーエムシー出版
• [Book] 生命への鍵「ステロイド」-その研究に貢献した生化学者と臨床家たち- (2009)
  • Author(s): 竹田亮祐、宮森勇、山本博
  • Publisher: (株)前田書店
• [Book] The mosaic evolution of the pancreatic polypeptide gene 107-124 Molecular biology of the islets Langerhans (2008)
  • Author(s): Yamamoto H, Yonekura H, Nata K
  • Publisher: digitally printed ver.
• [Remarks] ホームページ等
  • URL: http://maeda-shoten.com/yamamoto/index
• [Patent(Industrial Property Rights)] esRAGE過剰発現マウ (2009)
  • Inventor(s): 渡邉琢夫、山本博、山本靖彦、棟居聖一、杉原崇大、米倉秀人
  • Industrial Property Rights Holder: 国立大学法人金沢大学
  • Industrial Property Number: 特願,2009-120572
  • Filing Date: 2009-05-19
• [Patent(Industrial Property Rights)] RAGE遺伝子の2種類のスプライシングバリアントを区別して増幅可能なプライマリーセット及びプローブ (2009)
  • Inventor(s): 山本博、米倉秀人、渡邉琢夫、山本董彦、棟居聖一、大江和代
  • Industrial Property Rights Holder: 国立大学法人金沢大学
  • Industrial Property Number: 特願,2009-087418
  • Filing Date: 2009-03-31