本態性高血圧症因候補遺伝子の探索
著者 米倉 秀人
著者別表示 Yonekura Hideto
雑誌名 平成11(1999)年度 科学研究費補助金 基盤研究(C) 研究成果報告書概要
巻 1998 1999
ページ 4p.
発行年 2001‑10‑22
URL http://doi.org/10.24517/00064046
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http://creativecommons.org/licenses/by‑nc‑nd/3.0/deed.ja
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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 Type
Single-year Grants
Section
⼀般
Research Field
General medical chemistry
Research Institution
Kanazawa 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
Keywords
hypertension / 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
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(48 results)All Other All Publications 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.
[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)
[Publications] Ogawa, H.: "Functional properties of the unc-64 gene encoding a Caenorhabditis elegans syntaxin"J. Biol. Chem.. 273(4). 2192-2198 (1998)
[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)
[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)
[Publications] Nomura, M.: "Placenta growth factor (PIGF) mRNA expression in brain tumors"J Neurooncol.. 40(2). 123-130 (1998)
[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) [Publications] Wada, K.: "Cloning of three Caenorhabditis elegans genes potentially encoding novel matrix metalloproteinases"Gene. 211(1). 57-62 (1998)
[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)
[Publications] Yamagishi, S.: "AGE and endothelial cells"Journal of Atherosclerosis and Thrombosis. 4(4). 141-143 (1998)
[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)
[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)
[Publications] Yamagishi, S.: "Vascular endothelial growth factor acts as a pericyte mitogen under hypoxic conditions"Lab. Invest.. 79(4). 501-509 (1999)
[Publications] Yamagishi, S.: "Advanced glycation endoproducts accelerate calcification in microvascular pericytes"Biochem. Biophys. Res. Commun.. 258(2). 353-357
(1999)
[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)
[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)
[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)
[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)
[Publications] Abedin, Md. J.: "Molecular heterogeneity of the receptor for advanced glycation endproducts"J. Biochem. Mol. Biol. Biophys.. (in press). (2000) [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) [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)
[Publications] 卯⽊浩之: "AGEレセプター"臨床検査(医学書院). 44(3). 285-288 (2000)
[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)
[Publications] Unoki, H.: "Cyr61 is upregulated in aortic smooth muscle cells of spontaneously hypertensive rats"Arterioscl. Tnrom. Vas. Biol.. (acceptable pending
revision). (2000)
[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)
[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)
[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)
[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、野⼝⺠夫 編(南⼭堂). 131 (2000)
[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)
[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)
[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)
[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)
[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)
[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)
[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)
[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)
[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) [Publications] Yamagishi, S., Yonekura, H., Yamamoto, Y., Fujimori, H., Yamamoto, H.: "AGE and Endothelial Cell"J. Atheroscl. Thromb.. 4(4). 141-143 (1998)
[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)
[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)
[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)
[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)
[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)
[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)
[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)
[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)
Published: 2001-10-22 URL: https://kaken.nii.ac.jp/report/KAKENHI-PROJECT-10670116/106701161999kenkyu_seika_hokoku_
[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)
[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)
[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.).
