Functional analysis of LOXL-1 in the myocardium
| Project/Area Number |
18590792
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Circulatory organs internal medicine
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| Research Institution | Kurume University |
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Principal Investigator |
UEDA Tamenobu (2007) Kurume University, School of Medicine, Research Associate (50389251)
岡 直樹 (2006) 久留米大学, 医学部, 講師 (00299421)
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| Co-Investigator(Kenkyū-buntansha) |
KOGA Akimasa Kurume University, School of Medicine, Research Associate (10309776)
MIYAZAKI Hiroshi Kurume University, School of Medicine, Research Associate (90343699)
上田 集宣 久留米大学, 医学部, 助手 (50389251)
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| Project Period (FY) |
2006 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥4,010,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥510,000)
Fiscal Year 2007: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2006: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Keywords | Cardiac Hypertrophy / Lysyl oxydase / collagen / LOXL / fibrosis / 心肥大 / 活性酸素種 / 心筋 / トランスジェニックマウス |
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| Research Abstract |
It has been suggested that collagen cross-linking is present in hypertrophied myocardium. Lysyl oxidase (LOX) is a copper-dependent enzyme that initiates the cross-linking of collagens and elastin. Although it has been shown that five isoforms of LOX family members including lysyl oxidase-like protein-1 (LOXL1) are expressed in the heart, little is known about the role of LOXL1 in the heart. In this study, we investigated the role of LOXL1 in the development of cardiac hypertrophy in mice. We previously found that LOXL1 and B-type natriuretic peptide (BNP) mRNA were upregulated both in pressure and volume overload-induced hypertrophied myocardium by genechip analysis. In the present study, we examined the time course expression of LOXL1 in the heart during pressure overload. Real-time quantitative PCR revealed that that LOXL1 mRNA expression was upregulated in the hypertropic phase after aortic banding. To clarify roles of LOXL1 in a heart, we generated transgenic mice with cardiac-spe
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cific expression of LOXL1. Pups of LOXL1 transgenic mice (LOXL1-TG) were born normally and grew to adulthood without increased mortality. The left ventricle to body weight ratio was significantly increased in LOXL1-TG compared with WT littermates (WT). The echocardiography revealed that LOXL1-TG showed normal cardiac contraction but significant cardiac hypertrophy compared with type WT mice. The expression of BNP in the heart was 5.6-fold higher in LOXL1-TG than WT mice. Microscopic analysis also showed myocyte hypertrophy and mild interstitial fibrosis. Next, we examined the effect of hypertrophic agonists on the expression of LOXL1 in rat neonatal cardiomyocytes. Real-time quantitative PCR revealed that angiotensin II, norepinephrine and endothelin-1 significantly upregulated LOXL1 mRNA expression in cardiomyocytes. In addition, we found that LOX inhibitor, beta-aminopropionitrile, significantly inhibited these hypertrophic agonist-induced leucine incorporation in cardiomyocytes. These results suggest that LOXL1 is a cardiac hypertrophy promoting gene in mice. Less
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Report
(3 results)
Research Products
(15 results)
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[Journal Article] Pulmonary inflammation and enphysema. Role of cytokines IL-18 and IL-13.2007
Author(s)
Hoshino T, Kato S, Oka N, Imaoka H, Kinoshita T, Takei S, KitasatoY, Kawayama T, Imaizumi T, Yamada K, Young HA, Aizawa H
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Journal Title
Am JRespir Grit Care Med 176
Pages: 49-62
Description
「研究成果報告書概要(欧文)」より
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