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1999 Fiscal Year Final Research Report Summary

Screening for candidate genes involves in essential hypertension

Research Project

Project/Area Number 10670116
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field General medical chemistry
Research InstitutionKanazawa University

Principal Investigator

YONEKURA Hideto  School of Medicine, Biochemistry, Kanazawa University Associate Professor, 医学部, 助教授 (80240373)

Co-Investigator(Kenkyū-buntansha) YAMAMOTO Hiroshi  School of Medicine, Biochemistry, Kanazawa University Professor, 医学部, 教授 (00115198)
Project Period (FY) 1998 – 1999
Keywordshypertension / differential display / spontaneously hypertensive rat / cyr61 / in situ hybridization / quantitative trait locus
Research Abstract

For the study of essential hypertension, spontaneously hypertensive rats (SHR) and stroke-prone spontaneously hypertensive rats (SHRSP) have proven to be valuable models. In the present study, we applied a fluorescent differential display method to mRNAs from aortae of SHR, SHRSP and their parental strain, Wistar Kyoto rats (WKY) towards identifying the genes involved in the development of the hypertension, and came across a gene which is consistently upregulated in the hypertensive rats. Nucleotide sequence determination of the corresponding cDNA revealed that the gene is the rat orthologue of cyr61. Northern blot analysis showed that cyr61 expression increases in SHR and SHRSP before the onset of hypertension, and is sustained thereafter at higher levels than in age-matched WKY. In situ hybridization analysis demonstrated that cyr61 is expressed strongly in smooth muscle cells in media, and faintly in fibroblasts in adventitia, of the hypertensive rat aorta, while in WKY the expression is only in fibroblasts. Fluorescent in situ hybridization mapped the cyr61 gene to rat chromosome 1p12-13, which has not been previously reported as a quantitative trait locus for blood pressure regulation. These results suggest that cyr61 is an additional factor which may be involved in the development of systemic hypertension.

  • Research Products

    (48 results)

All Other

All Publications (48 results)

  • [Publications] Takamura, T.: "Transgenic mice overexpressing type 2 nitric oxide synthase in pancreatic b cells develop insulin-dependent diabetes without insulitis"J. Biol. Chem.. 273(5). 2493-2496 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ogawa, H.: "Functional properties of the unc-64 gene encoding a Caenorhabditis elegans syntaxin"J. Biol. Chem.. 273(4). 2192-2198 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yamagishi, S.: "Advanced glycation endproducts inhibit prostacyclin production and induce plasminogen activator inhibitor-1 in human microvascular endothelial cells"Diabetologica. 41(12). 1435-1441 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Segawa, Y.: "Upregulation of retinal vascular endothelial growth factor mRNAs in spontaneously diabetic rats without ophthalmoscopic retinopathy"Ophthalmic Res. 30(6). 333-339 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Nomura, M.: "Placenta growth factor (PIGF) mRNA expression in brain tumors"J Neurooncol.. 40(2). 123-130 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Taniguchi, K.: "The relation between the growth patterns of gastric carcinoma and the expression of hepatocyte growth factor receptor (c-met), autocrine motility factor receptor, and urokinase-type plasminogen activator receptor"Cancer. 82(11). 2112-2122 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Wada, K.: "Cloning of three Caenorhabditis elegans genes potentially encoding novel matrix metalloproteinases"Gene. 211(1). 57-62 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Tsugawa, K.: "Amplification of the c-met, c-erbB-2 and epidermal growth factor receptor gene in human gastric cancers : correlation to clinical features"Oncology. 55(5). 475-481 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yamagishi, S.: "AGE and endothelial cells"Journal of Atherosclerosis and Thrombosis. 4(4). 141-143 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yonekura, H.: "Placenta growth factor and vascular endothelial growth factor B and C expression in microvascular endothelial cells and pericytes : implication in autocrine and paracrine regulation of angiogenesis"J. Biol. Chem.. 274(49). 35172-35178 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yonekura, H.: "Antisense display-a method for functional gene screening : evaluation in a cell-free system and isolation of angiogenesis-related genes"Nucleic Acids Res.. 27(13). 2591-2600 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yamagishi, S.: "Vascular endothelial growth factor acts as a pericyte mitogen under hypoxic conditions"Lab. Invest.. 79(4). 501-509 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yamagishi, S.: "Advanced glycation endoproducts accelerate calcification in microvascular pericytes"Biochem. Biophys. Res. Commun.. 258(2). 353-357 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yamagishi, S.: "Insulin stimulates the growth and tube formation of human microvascular endothelial cells through autocrine vascular endothelial growth factor"Microvasc Res.. 57(3). 329-339 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Nakajima M.: "Deficient cotinine formation from nicotine is attributed to the whole deletion of the CYP2A6 gene in humans"Clin. Pharmacol. Ther.. 67(1). 57-69 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kusano, Y: "Participation of syndecan 2 in the induction of stress fiber formation in cooperation with integrin alfa 5 beta 1 : Structural characteristics of heparan sulphate chains with avidity to COOH-terminal heparin-binding domain of fibronectin"Exp. Cell Res.. (in press). (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Harada, S.: "Effects of ELF high magnetic fields on enzyme-catalyzed DNA and RNA synthesis in vitro and on a cell-free mismatch repair"Bioelectromagnetics. (in press). (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Abedin, Md. J.: "Molecular heterogeneity of the receptor for advanced glycation endproducts"J. Biochem. Mol. Biol. Biophys.. (in press). (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yamamoto, Y.: "Roles of the AGE-RAGE system in vascular injury in diabetes"Ann. N. Y. Acad. Sci. (Atherosclerosis V). 902(in press). (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 米倉秀人: "新しい機能性遺伝子スクリーニング法―Antisense Display法―の開発"Antisense(アンチセンスDNA/RNA研究会報). 3(2). 42-56 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 卯木浩之: "AGEレセプター"臨床検査(医学書院). 44(3). 285-288 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 田中伸茂: "AGE-RAGE系制御による糖尿病合併症防止の可能性について"内分泌・糖尿病科(科学評論社). 9(3). 261-266 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Unoki, H.: "Cyr61 is upregulated in aortic smooth muscle cells of spontaneously hypertensive rats"Arterioscl. Tnrom. Vas. Biol.. (acceptable pending revision). (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 米倉秀人: "KEY WORD 1998-2000 高血圧症・動脈硬化"斎藤 康、萩原俊男、馬渕 宏編(先端医学社). 207(48-49) (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 山岸昌一: "実験医学「血管の分子医学その最前線」"北 徹、山田信博、宮園浩平 編(羊土社). 208(188-191) (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 藤森 英希: "『血管と内皮』特集:内皮のストレスとその応答 AGEと内皮応答"メディカルレビュー社. 100 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 米倉秀人: "「医学のための基礎分子細胞生物学」第2版(36章、43章分担)"平賀紘一、山本博、伊達孝保、野口民夫 編(南山堂). 131 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 山本靖彦: "実験医学増刊"血管研究の最前線2000""北徹、佐藤靖史、永井良三 編(羊土社). 201(107-110) (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Takamura, T., Kato, I., Kimura, N., Nakazawa, T., Yonekura, H., Takasawa, S., Okamoto, H.: "Transgenic mice overexpressing type 2 nitric oxide synthase in pancreatic β cells develop insulin-dependent diabetes without insulitis."J. Biol. Chem.. 273(5). 2493-2496 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ogawa, H., Harada, S., Sassa, T., Yamamoto, H., Hosono, R.: "Functional properties of the unc-64 gene encoding a Caenorhabditis elegans syntaxin."J. Biol. Chem.. 273(4). 2192-2198 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yamagishi, S., Fujimori, H., Yonekura, ., Yamamoto, Y., Yamamoto, H.: "Advanced glycation endproducts inhibit prostacyclin production and induce plasminogen activator inhibitor-1 in human microvascular endothelial cells."Diabetologia. 41(12). 1435-1441 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Wada, K., Sato, H., Kinoh, H., Kajita, M., Yamamoto, H., Seiki, M.: "Cloning of three Caenorhabditis elegans genes potentially encoding novel matrix metalloproteinases."Gene. 211(1). 57-62 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Taniguchi, K., Yonemura, Y., Nojima, N., Hirono, Y., Fushida, S., Fujimura, T., Miwa, K., Endo, Y., Yamamoto, H., Watanabe, H.: "The relation between the growth patterns of gastric carcinoma and the expression of hepatocyte growth factor receptor (c-met), autocrine motility factor receptor, and urokinase-type plasminogen activator receptor."Cancer. 82(11). 2112-2122 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nomura, M., Yamagishi, S., Harada, S., Yamashima, T., Yamashita, J., Yamamoto, H.: "Placenta growth factor (PIGF) mRNA expression in brain tumors."J. Neurooncol.. 40(2). 123-130 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Segawa, Y., Shirao, Y., Yamagishi, S., Higashida, T., Kobayashi, M., Katsuno, K., Iyobe, A., Harada, H., Sato, F., Miyata, H., Asai, H., Nishimura, A., Takahira, M., Souno, T., Segawa, Y., Maeda, K., Shima, K., Mizuno, A., Yamamoto, H., Kawasaki, K.: "Upregulation of retinal vascular endothelial growth factor mRNAs in spontaneously diabetic rats without ophthalmoscopic retinopathy."Ophthalmic Res. 30(6). 333-339 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Tsugawa, K., Yonemura, Y., Hirono, Y., Fushida, S., Kaji, M., Miwa, K., Miyazaki, I., Yamamoto, H.: "Amplification of the c-met, c-erbB-2 and epidermal growth factor receptor gene in human gastric cancers : correlation to clinical features."Oncology. 55(5). 475-481 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yamagishi, S., Yonekura, H., Yamamoto, Y., Fujimori, H., Yamamoto, H.: "AGE and Endothelial Cell"J. Atheroscl. Thromb.. 4(4). 141-143 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yonekura, H., Sakurai, S., Liu, X., Migita, H., Wang, H., Yamagishi, S., Nomura, M., Abedin, Md. J., Unoki, H., Yamamoto, Y., Yamamoto, H.: "Placenta growth factor, VEGF-B and -C expressions in microvascular endothelial cells and pericytes : implication in autocrine and paracrine regulation of angiogenesis."J. Biol. Chem.. 274(49). 35172-35178 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yonekura, H., Migita, H., Sakurai, S., Harada, S., Yamagishi, S., Yamamoto, H.: "Antisense display - a method for functional gene screening : evaluation in a cell-free system and isolation of angiogenesis - related genes."Necleic Acids Res.. 27(13). 2591-2600 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yamagishi, S., Yonekura, H., Yamamoto, Y., Fujimori, H., Sakurai, S., Tanaka, N., Yamamoto H.: "Vascular endothelial growth factor acts as pericyte mitogen under hypoxic conditions."Lab. Invest.. 79(4). 501-509 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yamagishi, S., Fujimori, H., Yonekura, H., Tanaka, N., Yamamoto, H.: "Advanced glycation endproducts accelerate calcification in microvascular pericytes."Biochem. Biophys. Res. Commun.. 258(2). 353-357 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yamagishi, S., Kawakami, T., Fujimori, H., Yonekura, H., Tanaka, N., Yamamoto, Y., Urayama, H., Watanabe, Y., Yamamoto, H.: "Insulin stimulates the growth and tube formation of human microvascular endothelial cells through autocrine vascular endothelial growth factor."Microvasc Res.. 57(3). 329-339 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nakajima, M., Yamagishi, S., Yamamoto, H., Yamamoto, T., Kuroiwa, Y., Yokoi, T.: "Deficient cotinine formation from nicotine is ascribed to the whole deletion of the CYP2A6 gene in humans"Clin. Pharmacol. Ther.. 67(1). 57-69 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kusano, Y, Oguri, K., Nagayasu, Y., Munesue, S., Ishihara, M., Saiki, I, Yonekura, H., Yamamoto, H., Okayama, M.: "Participation of syndecan 2 in the induction of stress fiber formation in cooperation with integrin alfa 5 beta 1 : Structural characteristics of heparan sulphate chains with avidity to COOH-terminal heparin-binding domain of fibronectin."Exp. Cell Res.. (in press). (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Harada, S., Yamada, S., Kuramata, O., Gunnji, Y., Kawaaki, M., Miyakawa, T., Yonekura, H., Sakurai, S., Bessho, K., Hosono, R., Yamamoto, H.: "Effects of ELF high magnetic fields on enzyme-catalyzed DNA and RNA synthesis in vitro and on a cell-free mismatch repair."Bioelectromagnetics. (in press). (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Abedin, M. J., Yonekura, H., Karasawa, J., Migita, H., Yamamoto, Y., Yamamoto, H.: "Molecular heterogeneity of the receptor for advanced glycation endproducts."J. Biochem. Mol. Biol. Biophys.. (in press). (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yamamoto, Y., Yamagishi, S., Yonekura, H., Doi, T., Tsuji, H., Kato, I., Takasawa, S., Okamoto, H., MD. Joynal Abedin, Tanaka, N., Sakurai, S., Migita, H., Unoki, H., Wang, H., Zenda, Wu, P-S, Segawa, Y., Higashide, T., Kawasaki, K., Yamamoto, H.: "Roles of the AGE-RAGE system in vascular injury in diabetes atherosclerosis."Ann. N. Y. Acad. Sci. 902 (Atherosclerosis V). (in press). (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Unoki, H., Furukawa, K., Yonekura, H., Ueda, Y., Katsuta, S., Aono, H., Yamamoto, Y., Nakagawara, K., Mabuchi, H., Yamamoto, H.: "Cyr61 is upregulated in aortic smooth muscle cells of spontaeously hypertensive rats."Arterioscl. Throm. Vas. Biol.. (acceptable pending revision.).

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2001-10-23  

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