1995 Fiscal Year Annual Research Report

エンドセリン受容体の遺伝子転写調節機構と細胞増殖・接着における意義に関する研究

Research Project

Project/Area Number	07671130
Research Institution	Kyoto University
Principal Investigator	吉政孝明京都大学, 医学研究科, 助手 (00252429)
Co-Investigator(Kenkyū-buntansha)	荒井宏司京都大学, 医学研究科, 助手 (00263088)
Keywords	エンドセリン / エンドセリン受容体 / 転写 / シス配列 / RNAスプライシング
Research Abstract	1.エンドセリン(ET)受容体遺伝子の転写調節機構の解析: ヒトET-A受容体遺伝子5′隣接領域のfunctional assayを用いた検討により、-0.2kb〜-857b間に負の転写調節領域の、-137b〜-53b間及び-53b〜+251b間に正の転写調節領域の存在を明らかにした。更に、-137b〜-53bの正の転写調節領域をA7r5核抽出物を用いたゲルシャフトアッセイより解析した結果、-106b〜-78b間に核蛋白の結合を認めた。フットプリントアッセイの結果、-91b〜-83b間にCCCCACCTTからなる核蛋白結合部位を認めた。このようにET-A受容体遺伝子のbasal transcriptional activityには新しいシス配列が関与していることが示唆された。 2.エンドセリン-A受容体遺伝子alternative RNA splicingの遺伝子発現調節機構における関与の検討: ヒト肺total RNAをET-A受容体cDNAの全翻訳領域を増幅するプライマーを用いたRT-PCRを行うと、予想されるET-A受容体転写産物以外にbandsを認めた。これらに対するクローンをクローニングすると、それぞれエクソン4あるいはエクソン3,4がsplice outされたアイソホームであった。ET-A受容体遺伝子発現調節機構の一つを示唆するものと思われた。

Research Products
(21 results)

All Other

All Publications (21 results)

[Publications] J. Yamashita et al.: "Cis elements for transcriptional regulation of the human endothelin-A receptor gene." J. Cardiovasc. Pharmacol.26(Suppl. 3). S26-S28 (1995)
[Publications] Y. Miyamoto et al.: "Multiple transcripts of human endothelin-A receptor gene detected by reverse transcription and the polymerase chain reaction." J. Cardiovasc. Pharmacol.26(Suppl. 3). S29-S31 (1995)
[Publications] Y. Miyamoto et al.: "Alternative RNA splicing of human endothelin-A receptor generates multiple transcripts." Biochemical J.(in press).
[Publications] J. Hiraoka et al.: "Augmented expression of the endothelin-A receptor gene in cultured mesangial cells from stroke-prove spontaneously hypertensive rats." Clinical and Experimental Pharmacology and Physiology. Suppl 1. S191-S192 (1995)
[Publications] O. Nakagawa et al.: "Gene expression of prostacyclin receptor in the hypertrophied heart of spontaneously hypertensive rats." Clinical and Experimental Pharmacology and Physiology. Suppl 1. S270-S272 (1995)
[Publications] O. Nakagawa et al.: "Gene regulation of brain natriuretic peptide in cardiocyte hypertrophy by α_1-adrenergic stimulation" Clinical and Experimental Pharmacology and Physiology. Suppl 1. S183-S185 (1995)
[Publications] I. Kishimoto et al.: "Endothelin-induced activation of mitogen-activated protein kinases in glomerular mesargial cells from normotensive and stroke-prone spontaneously hypertensive rats." Clinical and Experimental Pharmacology and Physiology. Suppl 1. S207-S208 (1995)
[Publications] M. Nakagawa et al.: "Preparation of a monoclonal antibody against mouse brain natriuretic peptide(BNP) and tissue distribution of BNP in mice." Clinical and Experimental Pharmacology and Physiology. Suppl 1. S186-S187 (1995)
[Publications] M. Goto et al.: "Altered gene expression of natriuretic peptide receptor subtypes in the K idnoy of stroke-prove spontaneously hypertensive rats." Clinical and Experimental Pharmacology and Physiology. Suppl 1. S177-S179 (1995)
[Publications] Y. Ogawa et al.: "Molecular biology and biochemistry of natriuretic peptide family." Clinical and Experimental Pharmacology and Physiology. 22. 49-53 (1995)
[Publications] N. Hama et al.: "Rapid ventricular induction of brain natriuretic gene expression in experimental acute myocardial infarction." Circulation. 92. 1558-1564 (1995)
[Publications] O. Nakagawa et al.: "Rapid transcription activation and early mRNA turnover of brain natriuretic peptide in cardiocyte hypertrophy-Evidence for brain natriuretic peptide as an “emergency cardiac normone against ventricular overload-." J. Clin. Invest.96. 1280-1287 (1995)
[Publications] H. Itoh at al.: "Significance of autocrine/paracrine network in renal vascular and mesangial growth." Jpn. Heart J.36. 501- (1995)
[Publications] Y. Ogawa et al.: "Structural organization and chromosomal assignment of the human prostacyclin receptor gene." Genomics. 27. 142-148 (1995)
[Publications] T. Ikeda et al.: "Natriuretic peptide receptors in human arterial and venous coronary bypass vessels and rabbit vern grafts." Hypertension. (in press).
[Publications] K. Doi et al.: "Vascular endothelial growth factor potently suppresses CNP secretion from endothelial cells." Hypertension. (in press).
[Publications] N. Tamura et al.: "cDNA cloning and gene expression of human type I alpha cGMP-dependent protein kinase." Hypertension. (in press).
[Publications] Y. Komatsu et al.: "Regulation of endothelial production of C-type natriuretic peptide in coculture with vascular smooth muscle cells-The role of vascular natriuretic peptide system in vascular growth inhibition." Cir. Res.(in press).
[Publications] T. Igaki et al.: "C-type natriuretic peptide in chronic renal failure and its action in humans." Kidney Int.(in press).
[Publications] T. Igaki et al.: "Insulin suppresses endothelial secretion of C-type natriuretic peptide, a novel endothelium-derived relaxing peptide." Diabetes. (in press).
[Publications] Y. Komatsu et al.: "Regulation of secretion and clearance of C-type natriuretic peptide in the interaction of vascular endothelial cells and smooth muscle cells." J. Hypertens.(in press).

1995 Fiscal Year Annual Research Report

エンドセリン受容体の遺伝子転写調節機構と細胞増殖・接着における意義に関する研究

Principal Investigator

吉政 孝明 京都大学, 医学研究科, 助手 (00252429)

Research Products

[Publications] J. Yamashita et al.: "Cis elements for transcriptional regulation of the human endothelin-A receptor gene." J. Cardiovasc. Pharmacol.26(Suppl. 3). S26-S28 (1995)

[Publications] Y. Miyamoto et al.: "Multiple transcripts of human endothelin-A receptor gene detected by reverse transcription and the polymerase chain reaction." J. Cardiovasc. Pharmacol.26(Suppl. 3). S29-S31 (1995)

[Publications] Y. Miyamoto et al.: "Alternative RNA splicing of human endothelin-A receptor generates multiple transcripts." Biochemical J.(in press).

[Publications] J. Hiraoka et al.: "Augmented expression of the endothelin-A receptor gene in cultured mesangial cells from stroke-prove spontaneously hypertensive rats." Clinical and Experimental Pharmacology and Physiology. Suppl 1. S191-S192 (1995)

[Publications] O. Nakagawa et al.: "Gene expression of prostacyclin receptor in the hypertrophied heart of spontaneously hypertensive rats." Clinical and Experimental Pharmacology and Physiology. Suppl 1. S270-S272 (1995)

[Publications] O. Nakagawa et al.: "Gene regulation of brain natriuretic peptide in cardiocyte hypertrophy by α_1-adrenergic stimulation" Clinical and Experimental Pharmacology and Physiology. Suppl 1. S183-S185 (1995)

[Publications] I. Kishimoto et al.: "Endothelin-induced activation of mitogen-activated protein kinases in glomerular mesargial cells from normotensive and stroke-prone spontaneously hypertensive rats." Clinical and Experimental Pharmacology and Physiology. Suppl 1. S207-S208 (1995)

[Publications] M. Nakagawa et al.: "Preparation of a monoclonal antibody against mouse brain natriuretic peptide(BNP) and tissue distribution of BNP in mice." Clinical and Experimental Pharmacology and Physiology. Suppl 1. S186-S187 (1995)

[Publications] M. Goto et al.: "Altered gene expression of natriuretic peptide receptor subtypes in the K idnoy of stroke-prove spontaneously hypertensive rats." Clinical and Experimental Pharmacology and Physiology. Suppl 1. S177-S179 (1995)

[Publications] Y. Ogawa et al.: "Molecular biology and biochemistry of natriuretic peptide family." Clinical and Experimental Pharmacology and Physiology. 22. 49-53 (1995)

[Publications] N. Hama et al.: "Rapid ventricular induction of brain natriuretic gene expression in experimental acute myocardial infarction." Circulation. 92. 1558-1564 (1995)

[Publications] O. Nakagawa et al.: "Rapid transcription activation and early mRNA turnover of brain natriuretic peptide in cardiocyte hypertrophy-Evidence for brain natriuretic peptide as an “emergency cardiac normone against ventricular overload-." J. Clin. Invest.96. 1280-1287 (1995)

[Publications] H. Itoh at al.: "Significance of autocrine/paracrine network in renal vascular and mesangial growth." Jpn. Heart J.36. 501- (1995)

[Publications] Y. Ogawa et al.: "Structural organization and chromosomal assignment of the human prostacyclin receptor gene." Genomics. 27. 142-148 (1995)

[Publications] T. Ikeda et al.: "Natriuretic peptide receptors in human arterial and venous coronary bypass vessels and rabbit vern grafts." Hypertension. (in press).

[Publications] K. Doi et al.: "Vascular endothelial growth factor potently suppresses CNP secretion from endothelial cells." Hypertension. (in press).

[Publications] N. Tamura et al.: "cDNA cloning and gene expression of human type I alpha cGMP-dependent protein kinase." Hypertension. (in press).

[Publications] Y. Komatsu et al.: "Regulation of endothelial production of C-type natriuretic peptide in coculture with vascular smooth muscle cells-The role of vascular natriuretic peptide system in vascular growth inhibition." Cir. Res.(in press).

[Publications] T. Igaki et al.: "C-type natriuretic peptide in chronic renal failure and its action in humans." Kidney Int.(in press).

[Publications] T. Igaki et al.: "Insulin suppresses endothelial secretion of C-type natriuretic peptide, a novel endothelium-derived relaxing peptide." Diabetes. (in press).

[Publications] Y. Komatsu et al.: "Regulation of secretion and clearance of C-type natriuretic peptide in the interaction of vascular endothelial cells and smooth muscle cells." J. Hypertens.(in press).

吉政孝明京都大学, 医学研究科, 助手 (00252429)