2000 年度実績報告書

遺伝子変異動物を用いた心血管リモデリングの分子機構に関する多施設共同研究

研究課題

研究課題/領域番号	11694265
研究機関	京都大学
研究代表者	中尾一和京都大学, 医学研究科, 教授 (00172263)
研究分担者	菅原照京都大学, 医学研究科, 助手 (00312223) 伊藤裕京都大学, 医学研究科, 講師 (40252457) 斎藤能彦京都大学, 医学研究科, 助教授 (30250260) 小川佳宏京都大学, 医学研究科, 助手 (70291424) 向山政志京都大学, 医学研究科, 助手 (40270558)
キーワード	心血管リモデリング / 血管作動性物質 / ノックアウトマウス / トランスジェニックマウス / ナトリウム利尿ペプチド / 線維化 / 心筋肥大 / 糸球体硬化
研究概要	近年心臓血管病変の病態生理は「心血管リモデリング」という新しい概念で理解されるようになってきた。我々はいち早く分子生物学的手法を導入し、心臓及び血管そのものから合成分泌される新しい血管作動性物質及びその受容体の同定とその作用機構を明らかにしてきた。本研究は、心血管リモデリングにおける血管作動性物質の意義に焦点を合わせ、分子生物学的手法及び発生工学的手法を駆使し、遺伝子変異動物(遺伝子過剰発現トランスジェニックマウス及び遺伝子欠損ノックアウトマウス)を作成する。更に、それら動物を交配し種々の条件下で解析することでin vivoの心血管リモデリングにおける心臓血管ホルモンの生理的意義を解明することをその目的とするものである。本研究課題によって以下の研究成果を得た。 (1)我々は強力な血管平滑筋弛緩作用を有するナトリウム利尿ペプチドのうちANP、BNPは心臓から分泌され、一方CNPが血管内皮細胞から分泌されることを明らかにした。我々は、今回BNPノックアウトマウス(k/o)を作成した。BNPk/oにおいて心筋の著しい線維化が認められた。また、ANP、アンジオテンシン変換酵素(ACE)、TGF-β3、コラーゲンIV遺伝子の発現亢進が認められた。 (2)BNPk/oに対しaortic bandingを施行し、心筋に対する圧負荷を行ったところ、BNPk/oの心筋線維化は更に増強された。以上より、BNPが心臓局所ホルモンとして心筋の線維化に対して抑制的に作用していることが証明された。 (3)テキサス大Garbersの開発したGC-A(ANP、BNPの受容体)k/oは、血圧上昇及び心筋肥大を認める。GarbersよりGC-Ak/oの供与を受け、我々が既に保有しているBNPトランスジェニックマウス(Tg)と交配した。BNP-Tgにおいては、内軟骨骨化の活性化による骨格の伸長を認める。得られたBNP-Tg/GC-A-/-において、血圧及び心筋肥大のフェノタイプは変化しなかったが、長管骨の伸長を認めた。この結果は、BNPが組織により異なった受容体を介して作用する可能性を示唆するものである。 (4)BNPTgを用いて、5/6腎摘による腎臓障害モデルを作成したところ、コントロールマウスに比べBNPTgでは、TGF-βの発現の抑制に伴う糸球体硬化の抑制が認められ、BNPが腎保護的に作用することが明らかとなった。 (5)CNPk/oを作成した。CNPk/oはBNPTgとは対照的に内軟骨骨化の障害、低身長を認め、更に早期死亡を認めた。 (6)コラーゲンIVプロモーターにCNP遺伝子を連結し、これをトランスジーンとして骨特異的CNP過剰発現Tgを作成した(CNP-bone Tg)。CNPTgはRNPTgと同様に長管骨の伸長を認め、CNPk/oはCNP-boneTgとの交配により正常の発育が得られ、早期死亡は認められなくなった。このCNP-boneTg/CNPk/oを用い、現在心血管リモデリングにおけるCNPの意義を解析中である。

研究成果
(63件)

すべてその他

すべて文献書誌 (63件)

[文献書誌] J.Yamashita et al.: "Flkl-positive cells derived from embryonic stem cells serve as vascular progenitors."Nature. 408. 92-6 (2000)
[文献書誌] H.Kobayashi et al.: "Mutation analysis of Gs α,adrenocorticotropin receptor and p53 genes in Japanese patients with adrenocortical neoplasmas : including a case of Gs αmutation."Endocr J. 47. 461-6 (2000)
[文献書誌] Y.Yamamoto et al.: "Constitutively active mitogen-activated protein kinase kinase increases GLUT1 expression and recruits both GLUT1 and GLUT4 at the cell surface in 3T3-L1 adipocytes."Diabetes. 49. 332-9 (2000)
[文献書誌] M.Shintani et al.: "Down-regulation of leptin by free fatty acids in rat adipocytes : Effects of triacsin C, palmitate and 2-bromopalmitate."Metabolism. 49. 326-30 (2000)
[文献書誌] T-H.Chun et al.: "Oxidative stress augments secretion of endothelium-derived relaxing peptides, C-type natriuretic peptide and adrenomedullin."J Hypertens. 18. 575-80 (2000)
[文献書誌] T.Nagae et al.: "Rat receptor-activity-modifying proteins (RAMPs) for adrenomedullin/CGRP receptor : Cloning and upregulation in obstructive nephropathy."Biochem Biophys Res Commun. 270. 89-93 (2000)
[文献書誌] N.Tamura et al.: "Cardiac fibrosis in mice lacking brain natriuretic peptide."Proc Natl Acad Sci USA. 97. 4239-44 (2000)
[文献書誌] E.Ogawa et al.: "Outside-in signaling of fibronectin stimulates cardiomyocyte hypertrophy in cultured neonatal rat ventricular myocytes."J Mol Cell Cardiol. 32. 765-76 (2000)
[文献書誌] Y.Sakuma et al.: "Crucial involvement of the EP4 subtype of prostaglandin E(PGE) receptor in osteoclast ormation by pro-inflammatory cytokines and lipopolysaccharide."J Bone Miner Res. 15. 218-27 (2000)
[文献書誌] Y.Moriyama et al.: "The plasma levels of dehydroepiandrosterone sulfate (DHEAS) are decreased in patients with chronic heart failure in proportion to the severity."J Clin Endocrinol Metab. 85. 1834-40 (2000)
[文献書誌] P-S.Gao et al.: "Variants of NOS1, NOS2, and NOS3 genes in asthmatics."Biochem Biophys Res Commun. 267. 761-3 (2000)
[文献書誌] N.Sawada et al.: "Inhibition of Rho-associated kinase results in suppression of neointimal formation of balloon-injured arteries."Circulation. 101. 2030-3 (2000)
[文献書誌] M.Aizawa-Abe et al.: "Pathophysiological role of leptin in obesity-related hypertension."J Clin Invest. 105. 1243-52 (2000)
[文献書誌] M.Kasahara et al.: "Ameliorated glomerular injury in mice overexpressing brain natriuretic peptide with renal ablation."J Am Soc Nephrol. 11. 1691-701 (2000)
[文献書誌] M.Suda et al.: "Prostaglandin E2 (PGE2) induces the c-fos and c-jun expressions via the EP1 subtype of PGE receptor in mouse osteoblastic MC3T3-E1 cells."Calcif Tissue Int. 66. 217-23 (2000)
[文献書誌] M.Suda et al.: "C-type natriuretic peptide/guanylate cyclase B system in rat osteogenic ROB-C26 cells and its down-regulation by dexamethazone."Calcif Tissue Int. 65. 472-8 (2000)
[文献書誌] M.Yoshimura et al.: "A T-786→C mutation in the 5'-flanking region of the endothelial nitric oxide synthase gene and coronary arterial vasomotility."Am J Cardiol. 85. 710-4 (2000)
[文献書誌] I.Hamanaka et al.: "Effects of cardiotrophin-1 on hemodynamics and endocrine function of the heart."Am J Physiol. 278. H388-96 (2000)
[文献書誌] S.Yura et al.: "Accelerated puberty and late-onset hypothalamic hypogonadism in female transgenic skinny mice overexpressing leptin."J Clin Invest. 105. 749-55 (2000)
[文献書誌] T.Usui et al.: "Functional significance of prop-1 gene expression in pituitary adenomas."Endocri J. 47. S85-9 (2000)
[文献書誌] M.Shintani et al.: "Down-regulation of leptin by free fatty acids in rat adipocytes : effects of triacsinC, palmitate and 2-bromopalmitate."Metabolism. 49. 326-30 (2000)
[文献書誌] M.Tanaka et al.: "Cloning of novel soluble gp130 and detection of its neutralizing autoantibodies in rheumatoid arthritis."J Clin Invest. 106. 137-44 (2000)
[文献書誌] H.Chusho et al.: "Genetic models reveal that brain natriuretic peptide can signal through different tissue-specific receptor-mediated pathways."Endocrinology. 141. 3807-13 (2000)
[文献書誌] W.Ma et al.: "Detection of anti-neutrophil cytoplasmic antibodies in MRL/Mp-lpr/lpr mice and analysis of their target antigens."Autoimmunity. 32. 281-91 (2000)
[文献書誌] Y.Miyamoto et al.: "Replication protein Al reduces transcription of the endothelial nitric oxide synthase gene containing a T-^<786>→C mutation associated with coronary spastic angina."Hum Mol Genet. 9. 2629-37 (2000)
[文献書誌] K.Yahata et al.: "Molecular cloning and expression of a novel klotho-related protein."J Mol Med. 78. 389-94 (2000)
[文献書誌] K.Nakao et al.: "Current topics in pheochromocytoma."Biomed & Pharmacother. 54. 124S-8S (2000)
[文献書誌] Y.Sakuma et al.: "Impaired bone resorption by lipopolysaccharide in vivo in mice deficient in the prostaglandin EP4 subtype."Infect Immun. 68. 6819-25 (2000)
[文献書誌] T.Akamizu et al.: "Images in thyroidology-air in the thyroid."Thyroid. 10. 519-20 (2000)
[文献書誌] T.Akamizu et al.: "Hashimoto's thyroiditis with heterogeneous antithyrotropin receptor antibodies : unique epitopes may contribute to the regulation of thyroid function by the antibodies."J Clin Endocrinol Metab. 85. 2116-21 (2000)
[文献書誌] K.Takaya et al.: "Ghrelin strongly stimulates growth hormone (GH) release in humans."J Clin Endocrinol Metab. 85. 4908-11 (2000)
[文献書誌] M.Yoshimura et al.: "Association of the missense Glu298Asp variant of the endothelial nitric oxide synthase gene with severe preeclampsia."J Soc Gynecol Investig. 7. 238-41 (2000)
[文献書誌] M.Yoshimura et al.: "Genetic risk factors for coronary artery spasm : significance of endothelial nitric oxide synthase gene T-^<786>→C and missense Glu298Asp variants."J Invest Med. 48. 367-74 (2000)
[文献書誌] K.Ikeda et al.: "Possible involvement of endothelin-1 in cardioprotective effects of benidipine."Hypertens Res. 23. 491-6 (2000)
[文献書誌] S.Asai et al.: "The heart is a source of circulating cardiotrophin-1 in humans."Biochem Biophys Res Commun. 279. 320-3 (2000)
[文献書誌] T.Akamizu et al.: "Association of autoimmune thyroid disease with microsatellite markers for the thyrotropin receptor gene and CTLA-4 in Japanese patients."Thyroid. 10. 851-8 (2000)
[文献書誌] N.Hirai et al.: "Insulin resistance and endothelial dysfunction in smokers : effects of vitamin C."Am J Physiol Heart Circ Playsiol. 279. H1172-8 (2000)
[文献書誌] M.Yoshimura et al.: "Interaction on metabolic clearance between A-type and B-type natriuretic peptides in patients with heart failure."Metabolism. 49. 1228-33 (2000)
[文献書誌] M.Kotani et al.: "Multiple signal transduction pathways through two prostaglandin E receptor EP3 subtype isoforms expressed in human uterus."J Clin Endocrinol Metab. 85. 4315-22 (2000)
[文献書誌] K.Mori et al.: "Disruption of klotho gene causes and abnormal energy homeostasis in mice."Biochem Biophys Res Commun. 278. 665-70 (2000)
[文献書誌] K.Mori et al.: "Kidney produces a novel acylated peptide,ghrelin."FEBS Lett. 486. 213-6 (2000)
[文献書誌] T.Akamizu et al.: "Images in thyroidology-Moisture chamber for management of corneal ulcer due to Grave's ophthalmopathy."Thyroid. 10. 1123-4 (2000)
[文献書誌] M.Nakayama et al.: "T-^<786>→C mutation in the 5'-flanking region of the endothelial nitric oxide synthase gene is associated with myocardial infarction, especially without coronary organic stenosis."Am J Cardiol. 86. 628-34 (2000)
[文献書誌] K.Kuwahara et al.: "Cardiotrophin-1 phosphorylates akt and BAD, and prolongs cell survival via a PI3K-dependent pathway in cardiac myocytes."J Mol Cell Cardiol. 32. 1385-94 (2000)
[文献書誌] Y.Mizuno et al.: "Secretion patterns of A-type and B-type natriuretic peptides in patients with hypertrophic cardiomyopathy or idiopathic cardiomyopathy."Am J Cardiol. 86. 1036-40 (2000)
[文献書誌] N.Kajiyama et al.: "Lack of association between T-^<786>→C mutation in the 5'-flanking region of the endothelial nitric oxide synthase gene and essential hypertension."Hypertens Res. 3. 561-5 (2000)
[文献書誌] S.Muro et al.: "Expression of prostaglandin E receptor EP4 subtype in rat adrenal zona glomerulosa : Involvement in aldosterone release."Endocr J. 47. 429-36 (2000)
[文献書誌] S.Sugo et al.: "Regulation of endothelin-1 production in cultured rat vascular smooth muscle cells."J Cardiovasc Pharmacol. 37. 25-40 (2001)
[文献書誌] N.Matsuoka et al.: "Decreased triglyceride-rich lipoproteins in transgenic skinny mice overexpressing leptin."Am J Physiol. 280. E334-9 (2001)
[文献書誌] T.Kuramoto et al.: "Attractin/mahogany/zitter plays a critical role in myelination of the central nervous system."Proc Natl Acad Sci USA. 98. 559-64 (2001)
[文献書誌] Y.Mizuno et al.: "Aldosterone production iactivated in the failing ventricles in humans."Circulation. 103. 72-7 (2001)
[文献書誌] N.Sawada et al.: "cGMP-dependent protein kinase phosphorylated and inactivates RhoA."Biochem Biophys Res Commun. 280. 798-805 (2001)
[文献書誌] M.Shintani et al.: "Ghrelin, an endogenous growth hormone secretagogue, is a novel orexigenic peptide that antagonizes leptin action through the activation of hypothalamic neuropeptide Y/Y1 receptor pathway."Diabetes. 50. 227-32 (2001)
[文献書誌] H.Azechi et al.: "Disruption of the RB pathway in the majority of human hepatocellular carcinomas."Oncology. (in press). (2001)
[文献書誌] M.Minata et al.: "Postoperative detection of AFP mRNA in blood as a predictor for metastatic recurrence of hepatocellular carcinoma."J Gastroenterol Hepatol. (in press). (2001)
[文献書誌] M.Inoue et al.: "Oxidized low density lipoprotein regulates VEGF expression in human macrophages and endothelial cells through activation of PPARγ."Arterioscler Thromb Vasc Biol. (in press). (2001)
[文献書誌] H.Chusho et al.: "Dwarfism and early death in mice lacking C-type natriuretic peptide."Proc Natl Acad Sci USA. (in press). (2001)
[文献書誌] K.Kuwahara et al.: "Neuron-restrictive silencer element/neuron-restrictive silencer factor system regulates basal-and endothelin-1-inducible atrial natriuretic peptide gene expression in ventricular myocytes."Mol Cell Biol. (in press). (2001)
[文献書誌] I.Hamanaka et al.: "Induction of JAB/SOCS-1/SSI-1 and CIS3/SOCS-3/SSI-3 is involved in gp130 resistance in cardiovascular system in rat treated with cardiotrophin-1 (CT-1) in vivo."Circ Res. (in press). (2001)
[文献書誌] Y.Fukunaga et al.: "Thiazolidinediones, peroxisome proliferator-activated receptor γ agonists, regulate endothelial cell growth and secretion of vasoactive peptides."Atherosclerosis. (in press). (2001)
[文献書誌] K.Doi et al.: "C-type natriuretic peptide induces re-differentiation of vascular smooth muscle cells with acceleratedre-endothelialization."Arterioscler Thromb Vasc Biol. (in press). (2001)
[文献書誌] T.Suganami et al.: "Altered growth response to prostaglandin E2 and its receptor signaling in mesangial cells from stroke-prone spontaneously hypertensive rats."J Hypertens. (in press). (2001)
[文献書誌] S.Yonemitsu et al.: "Troglitazone induces GLUT4 translocation in L6 myotubes."Diabetes. (in press). (2001)

2000 年度 実績報告書

遺伝子変異動物を用いた心血管リモデリングの分子機構に関する多施設共同研究

研究代表者

中尾 一和 京都大学, 医学研究科, 教授 (00172263)

研究成果

[文献書誌] J.Yamashita et al.: "Flkl-positive cells derived from embryonic stem cells serve as vascular progenitors."Nature. 408. 92-6 (2000)

[文献書誌] H.Kobayashi et al.: "Mutation analysis of Gs α,adrenocorticotropin receptor and p53 genes in Japanese patients with adrenocortical neoplasmas : including a case of Gs αmutation."Endocr J. 47. 461-6 (2000)

[文献書誌] Y.Yamamoto et al.: "Constitutively active mitogen-activated protein kinase kinase increases GLUT1 expression and recruits both GLUT1 and GLUT4 at the cell surface in 3T3-L1 adipocytes."Diabetes. 49. 332-9 (2000)

[文献書誌] M.Shintani et al.: "Down-regulation of leptin by free fatty acids in rat adipocytes : Effects of triacsin C, palmitate and 2-bromopalmitate."Metabolism. 49. 326-30 (2000)

[文献書誌] T-H.Chun et al.: "Oxidative stress augments secretion of endothelium-derived relaxing peptides, C-type natriuretic peptide and adrenomedullin."J Hypertens. 18. 575-80 (2000)

[文献書誌] T.Nagae et al.: "Rat receptor-activity-modifying proteins (RAMPs) for adrenomedullin/CGRP receptor : Cloning and upregulation in obstructive nephropathy."Biochem Biophys Res Commun. 270. 89-93 (2000)

[文献書誌] N.Tamura et al.: "Cardiac fibrosis in mice lacking brain natriuretic peptide."Proc Natl Acad Sci USA. 97. 4239-44 (2000)

[文献書誌] E.Ogawa et al.: "Outside-in signaling of fibronectin stimulates cardiomyocyte hypertrophy in cultured neonatal rat ventricular myocytes."J Mol Cell Cardiol. 32. 765-76 (2000)

[文献書誌] Y.Sakuma et al.: "Crucial involvement of the EP4 subtype of prostaglandin E(PGE) receptor in osteoclast ormation by pro-inflammatory cytokines and lipopolysaccharide."J Bone Miner Res. 15. 218-27 (2000)

[文献書誌] Y.Moriyama et al.: "The plasma levels of dehydroepiandrosterone sulfate (DHEAS) are decreased in patients with chronic heart failure in proportion to the severity."J Clin Endocrinol Metab. 85. 1834-40 (2000)

[文献書誌] P-S.Gao et al.: "Variants of NOS1, NOS2, and NOS3 genes in asthmatics."Biochem Biophys Res Commun. 267. 761-3 (2000)

[文献書誌] N.Sawada et al.: "Inhibition of Rho-associated kinase results in suppression of neointimal formation of balloon-injured arteries."Circulation. 101. 2030-3 (2000)

[文献書誌] M.Aizawa-Abe et al.: "Pathophysiological role of leptin in obesity-related hypertension."J Clin Invest. 105. 1243-52 (2000)

[文献書誌] M.Kasahara et al.: "Ameliorated glomerular injury in mice overexpressing brain natriuretic peptide with renal ablation."J Am Soc Nephrol. 11. 1691-701 (2000)

[文献書誌] M.Suda et al.: "Prostaglandin E2 (PGE2) induces the c-fos and c-jun expressions via the EP1 subtype of PGE receptor in mouse osteoblastic MC3T3-E1 cells."Calcif Tissue Int. 66. 217-23 (2000)

[文献書誌] M.Suda et al.: "C-type natriuretic peptide/guanylate cyclase B system in rat osteogenic ROB-C26 cells and its down-regulation by dexamethazone."Calcif Tissue Int. 65. 472-8 (2000)

[文献書誌] M.Yoshimura et al.: "A T-786→C mutation in the 5'-flanking region of the endothelial nitric oxide synthase gene and coronary arterial vasomotility."Am J Cardiol. 85. 710-4 (2000)

[文献書誌] I.Hamanaka et al.: "Effects of cardiotrophin-1 on hemodynamics and endocrine function of the heart."Am J Physiol. 278. H388-96 (2000)

[文献書誌] S.Yura et al.: "Accelerated puberty and late-onset hypothalamic hypogonadism in female transgenic skinny mice overexpressing leptin."J Clin Invest. 105. 749-55 (2000)

[文献書誌] T.Usui et al.: "Functional significance of prop-1 gene expression in pituitary adenomas."Endocri J. 47. S85-9 (2000)

[文献書誌] M.Shintani et al.: "Down-regulation of leptin by free fatty acids in rat adipocytes : effects of triacsinC, palmitate and 2-bromopalmitate."Metabolism. 49. 326-30 (2000)

[文献書誌] M.Tanaka et al.: "Cloning of novel soluble gp130 and detection of its neutralizing autoantibodies in rheumatoid arthritis."J Clin Invest. 106. 137-44 (2000)

[文献書誌] H.Chusho et al.: "Genetic models reveal that brain natriuretic peptide can signal through different tissue-specific receptor-mediated pathways."Endocrinology. 141. 3807-13 (2000)

[文献書誌] W.Ma et al.: "Detection of anti-neutrophil cytoplasmic antibodies in MRL/Mp-lpr/lpr mice and analysis of their target antigens."Autoimmunity. 32. 281-91 (2000)

[文献書誌] Y.Miyamoto et al.: "Replication protein Al reduces transcription of the endothelial nitric oxide synthase gene containing a T-^<786>→C mutation associated with coronary spastic angina."Hum Mol Genet. 9. 2629-37 (2000)

[文献書誌] K.Yahata et al.: "Molecular cloning and expression of a novel klotho-related protein."J Mol Med. 78. 389-94 (2000)

[文献書誌] K.Nakao et al.: "Current topics in pheochromocytoma."Biomed & Pharmacother. 54. 124S-8S (2000)

[文献書誌] Y.Sakuma et al.: "Impaired bone resorption by lipopolysaccharide in vivo in mice deficient in the prostaglandin EP4 subtype."Infect Immun. 68. 6819-25 (2000)

[文献書誌] T.Akamizu et al.: "Images in thyroidology-air in the thyroid."Thyroid. 10. 519-20 (2000)

[文献書誌] T.Akamizu et al.: "Hashimoto's thyroiditis with heterogeneous antithyrotropin receptor antibodies : unique epitopes may contribute to the regulation of thyroid function by the antibodies."J Clin Endocrinol Metab. 85. 2116-21 (2000)

[文献書誌] K.Takaya et al.: "Ghrelin strongly stimulates growth hormone (GH) release in humans."J Clin Endocrinol Metab. 85. 4908-11 (2000)

[文献書誌] M.Yoshimura et al.: "Association of the missense Glu298Asp variant of the endothelial nitric oxide synthase gene with severe preeclampsia."J Soc Gynecol Investig. 7. 238-41 (2000)

[文献書誌] M.Yoshimura et al.: "Genetic risk factors for coronary artery spasm : significance of endothelial nitric oxide synthase gene T-^<786>→C and missense Glu298Asp variants."J Invest Med. 48. 367-74 (2000)

[文献書誌] K.Ikeda et al.: "Possible involvement of endothelin-1 in cardioprotective effects of benidipine."Hypertens Res. 23. 491-6 (2000)

[文献書誌] S.Asai et al.: "The heart is a source of circulating cardiotrophin-1 in humans."Biochem Biophys Res Commun. 279. 320-3 (2000)

[文献書誌] T.Akamizu et al.: "Association of autoimmune thyroid disease with microsatellite markers for the thyrotropin receptor gene and CTLA-4 in Japanese patients."Thyroid. 10. 851-8 (2000)

[文献書誌] N.Hirai et al.: "Insulin resistance and endothelial dysfunction in smokers : effects of vitamin C."Am J Physiol Heart Circ Playsiol. 279. H1172-8 (2000)

[文献書誌] M.Yoshimura et al.: "Interaction on metabolic clearance between A-type and B-type natriuretic peptides in patients with heart failure."Metabolism. 49. 1228-33 (2000)

[文献書誌] M.Kotani et al.: "Multiple signal transduction pathways through two prostaglandin E receptor EP3 subtype isoforms expressed in human uterus."J Clin Endocrinol Metab. 85. 4315-22 (2000)

[文献書誌] K.Mori et al.: "Disruption of klotho gene causes and abnormal energy homeostasis in mice."Biochem Biophys Res Commun. 278. 665-70 (2000)

[文献書誌] K.Mori et al.: "Kidney produces a novel acylated peptide,ghrelin."FEBS Lett. 486. 213-6 (2000)

[文献書誌] T.Akamizu et al.: "Images in thyroidology-Moisture chamber for management of corneal ulcer due to Grave's ophthalmopathy."Thyroid. 10. 1123-4 (2000)

[文献書誌] M.Nakayama et al.: "T-^<786>→C mutation in the 5'-flanking region of the endothelial nitric oxide synthase gene is associated with myocardial infarction, especially without coronary organic stenosis."Am J Cardiol. 86. 628-34 (2000)

[文献書誌] K.Kuwahara et al.: "Cardiotrophin-1 phosphorylates akt and BAD, and prolongs cell survival via a PI3K-dependent pathway in cardiac myocytes."J Mol Cell Cardiol. 32. 1385-94 (2000)

[文献書誌] Y.Mizuno et al.: "Secretion patterns of A-type and B-type natriuretic peptides in patients with hypertrophic cardiomyopathy or idiopathic cardiomyopathy."Am J Cardiol. 86. 1036-40 (2000)

[文献書誌] N.Kajiyama et al.: "Lack of association between T-^<786>→C mutation in the 5'-flanking region of the endothelial nitric oxide synthase gene and essential hypertension."Hypertens Res. 3. 561-5 (2000)

[文献書誌] S.Muro et al.: "Expression of prostaglandin E receptor EP4 subtype in rat adrenal zona glomerulosa : Involvement in aldosterone release."Endocr J. 47. 429-36 (2000)

[文献書誌] S.Sugo et al.: "Regulation of endothelin-1 production in cultured rat vascular smooth muscle cells."J Cardiovasc Pharmacol. 37. 25-40 (2001)

[文献書誌] N.Matsuoka et al.: "Decreased triglyceride-rich lipoproteins in transgenic skinny mice overexpressing leptin."Am J Physiol. 280. E334-9 (2001)

[文献書誌] T.Kuramoto et al.: "Attractin/mahogany/zitter plays a critical role in myelination of the central nervous system."Proc Natl Acad Sci USA. 98. 559-64 (2001)

[文献書誌] Y.Mizuno et al.: "Aldosterone production iactivated in the failing ventricles in humans."Circulation. 103. 72-7 (2001)

[文献書誌] N.Sawada et al.: "cGMP-dependent protein kinase phosphorylated and inactivates RhoA."Biochem Biophys Res Commun. 280. 798-805 (2001)

[文献書誌] M.Shintani et al.: "Ghrelin, an endogenous growth hormone secretagogue, is a novel orexigenic peptide that antagonizes leptin action through the activation of hypothalamic neuropeptide Y/Y1 receptor pathway."Diabetes. 50. 227-32 (2001)

[文献書誌] H.Azechi et al.: "Disruption of the RB pathway in the majority of human hepatocellular carcinomas."Oncology. (in press). (2001)

[文献書誌] M.Minata et al.: "Postoperative detection of AFP mRNA in blood as a predictor for metastatic recurrence of hepatocellular carcinoma."J Gastroenterol Hepatol. (in press). (2001)

[文献書誌] M.Inoue et al.: "Oxidized low density lipoprotein regulates VEGF expression in human macrophages and endothelial cells through activation of PPARγ."Arterioscler Thromb Vasc Biol. (in press). (2001)

[文献書誌] H.Chusho et al.: "Dwarfism and early death in mice lacking C-type natriuretic peptide."Proc Natl Acad Sci USA. (in press). (2001)

[文献書誌] K.Kuwahara et al.: "Neuron-restrictive silencer element/neuron-restrictive silencer factor system regulates basal-and endothelin-1-inducible atrial natriuretic peptide gene expression in ventricular myocytes."Mol Cell Biol. (in press). (2001)

[文献書誌] I.Hamanaka et al.: "Induction of JAB/SOCS-1/SSI-1 and CIS3/SOCS-3/SSI-3 is involved in gp130 resistance in cardiovascular system in rat treated with cardiotrophin-1 (CT-1) in vivo."Circ Res. (in press). (2001)

[文献書誌] Y.Fukunaga et al.: "Thiazolidinediones, peroxisome proliferator-activated receptor γ agonists, regulate endothelial cell growth and secretion of vasoactive peptides."Atherosclerosis. (in press). (2001)

[文献書誌] K.Doi et al.: "C-type natriuretic peptide induces re-differentiation of vascular smooth muscle cells with acceleratedre-endothelialization."Arterioscler Thromb Vasc Biol. (in press). (2001)

[文献書誌] T.Suganami et al.: "Altered growth response to prostaglandin E2 and its receptor signaling in mesangial cells from stroke-prone spontaneously hypertensive rats."J Hypertens. (in press). (2001)

[文献書誌] S.Yonemitsu et al.: "Troglitazone induces GLUT4 translocation in L6 myotubes."Diabetes. (in press). (2001)

2000 年度実績報告書

中尾一和京都大学, 医学研究科, 教授 (00172263)