2000 Fiscal Year Final Research Report Summary
Clinical implication of cardiovascular hormones
| Project/Area Number |
10307026
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| Research Category |
Grant-in-Aid for Scientific Research (A).
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Endocrinology
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| Research Institution | KYOTO UNIVERSITY |
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Principal Investigator |
NAKAO Kazuwa Kyoto Univ., Med. and Clin. Sci., Professor, 医学研究科, 教授 (00172263)
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| Co-Investigator(Kenkyū-buntansha) |
MUKOYAMA Masashi Kyoto Univ., Med. and Clin. Sci., Assistant Professor, 医学研究科, 助手 (40270558)
ITOH Hiroshi Kyoto Univ., Med. and Clin. Sci., Associate Professor, 医学研究科, 講師 (40252457)
SAITO Yoshihiko Kyoto Univ., Med. and Clin. Sci., Associate Professor, 医学研究科, 助教授 (30250260)
OGAWA Yoshihiro Kyoto Univ., Med. and Clin. Sci., Assistant Professor, 医学研究科, 助手 (70291424)
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| Project Period (FY) |
1998 – 2000
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| Keywords | CT-1 / BNP / CNP / knockout mice / cultured myocytes / cardiac fibrosis / endochondral ossification |
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| Research Abstract |
We previously reported that, using in vivo myocytes-nonmyocytes co-culture model, endothelin-1 secreted from nonmyocytes are involved in the process of cardiac hypertrophy. In this study, we examined a role of CT-1, a novel interleukin-6 related cytokine having ability to evoke cardiac cell hypertrophy, in the myocytes-nonmyocytes interaction in an in vitro model of cardiac hypertrophy. We showed that CT-1 plays a role in the hypertrophic process in the co-culture, suggesting a role of CT-1 as a local regulator during cardiac hypertrophy.
BNP is a cardiac hormonc produced primarily by ventricular myocytes. In this study, we generated mice with targeted disruption of BNP (BNP^<-/-> mice). We observed multifocal fibrotic lesions in the ventriceles from BNP^<-/-> mice. No signs of systemic hypertension and ventricular hypertrophy are noted in BNP^<-/-> mice. In response to ventricular pressure overload, focal fibrotic lesions are increased in size and number in BNP^<-/-> mice, whereas no f
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ocal fibrotic changes arc found in wild-type littermates. This study establishes BNP as a cardiomyocyte-derived antifibrotic factor in vivo and provides cvidence for its role as a local regulator of ventricular remodeling.
CNP occurs in a variety of central and peripheral tissues, where it acts as an autocrine and paracrinre regulator. In this study, we generated mice with targeted disruption of CNP(CNP^<-/-> mice).The CNP^<-/-> mice show severe dwarfism as a result of imparired endochondral ossification. They are all viable perinatally, but less than half can survive during postnatal developmcnt. The skeletal phenotypes are histologically similar to those seen in patients with achondroplasia, the most common genetic form of human dwarfism. Targeted expression of CNP in the growth plate chondrocytes can rescue the skeletal defect of CNP^<-/-> micc and allow their prolonged survival. This study demonstrates that CNP acts locally as a positive regulator of endochondral ossification in vivo and suggests its pathophysiological and therapcutic implication in some forms of skeletal dysplasia. Less
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[Publications] H.Chusho, N.Tamura, Y.Ogawa, A.Yasoda, M.Suda, T.Miyazawa, K.Nakamura, K.Nakao, T.Kurihara, Y.Komatsu, H.Itoh, K.Tanaka, Y.Saito, M.Katsuki, and K.Nakao: "Dwarfism and early death in mice lacking C-type natriuretic peptide."Proc.Natl.Acad.USA. (in press). (2001)
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「研究成果報告書概要(欧文)」より
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[Publications] K.Kuwahara, Y.Saito, E.Ogawa, N.Takahashi, Y.Nakagawa, Y.Naruse, M.Harada, I.Hamanaka, T.Izumi, Y.Miyamoto, I.Kishimoto, R.Kawakami, M.Nakanishi, N.Mori, and K.Nakao: "Neuron-restrictive silencer e1ement/neuron-restrictive silencer factor system regulates basal and endothelin-1-inducible atrial natriuretic peptide gene expression in ventricular myocytes."Mol.Cell.Biol.. 21. 2085-2097 (2001)
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「研究成果報告書概要(欧文)」より
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[Publications] H.Chusho, Y.Ogawa, N.Tamura, M.Suda, A.Yasoda, T.Miyazawa, I.Kishimoto, Y.Komatsu, H.Itoh, K.Tanaka, Y.Saito, D.L.Garbers, and K.Nakao: "Genetic models reveal that brain natriuretic peptide can signal through different tissue-specific receptor-mediated pathways."Endocrinology. 141. 3807-3813 (2000)
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「研究成果報告書概要(欧文)」より
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[Publications] N.Tamura, Y.Ogawa, H.Chusho, K.Nakamura, K.Nakao, M.Suda, M.Kasahara, R.Hashimoto, G.Katsuura, M.Mukoyama, H.Itoh, Y.Saito, I.Tanaka, H.Otani M.Katsuki, and K.Nakao: "Cardiac fibrosis in mice lacking brain natriuretic peptide."Proc.Natl.Acad.Sci.USA. 97. 4239-4244 (2000)
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「研究成果報告書概要(欧文)」より
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[Publications] M.Suda, Y.Ogawa, K.Tanaka, N.Tamura, A.Yasoda, T.Takigawa, M.Uehira, H.Nishimoto, H.Itoh, Y.Saito, K.Shiota, and K.Nakao: "Skeletal overgrowth in transgenic mice that overexpress brain natriuretic peptide."Proc.Natl.Acad.Sci.USA. 95. 2337-2342 (1998)
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「研究成果報告書概要(欧文)」より
