Pathophysiological roles of nardilysin, critical factor for axonal maturation and myelination
Project/Area Number |
23300117
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Research Category |
Grant-in-Aid for Scientific Research (B)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Neuroscience in general
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Research Institution | Kyoto University |
Principal Investigator |
NISHI Eiichiro 京都大学, 医学(系)研究科(研究院), 准教授 (30362528)
|
Co-Investigator(Kenkyū-buntansha) |
OHNO Mikiko 京都大学, 医学(系)研究科(研究院), 助教 (10583198)
平岡 義範 京都大学, 医学(系)研究科(研究院), 助教 (60397552)
|
Project Period (FY) |
2011-04-01 – 2014-03-31
|
Project Status |
Completed (Fiscal Year 2013)
|
Budget Amount *help |
¥20,020,000 (Direct Cost: ¥15,400,000、Indirect Cost: ¥4,620,000)
Fiscal Year 2013: ¥6,630,000 (Direct Cost: ¥5,100,000、Indirect Cost: ¥1,530,000)
Fiscal Year 2012: ¥6,760,000 (Direct Cost: ¥5,200,000、Indirect Cost: ¥1,560,000)
Fiscal Year 2011: ¥6,630,000 (Direct Cost: ¥5,100,000、Indirect Cost: ¥1,530,000)
|
Keywords | メタロプロテアーゼ / 髄鞘形成 / 交感神経 / 循環動態 / 細胞外ドメインシェディング / アルツハイマー病 / 多発性硬化症 / 徐脈 / 軸索成熟 / 低血圧 / BACE1 |
Research Abstract |
We originally identified a metalloendopeptidase nardylisin (NRDc) as a binding partner of HB-EGF and reported that NRDc enhances ectodomain shedding of multiple membrane proteins. We generated NRDc-deficient (Nrd1-/-) mice and demonstrated that NRDc critically regulates axonal maturation and myelination in the central and peripheral nervous system through the regulation of neuregulin-1 shedding. Here, we demonstrate that Nrd1-/- mice show severe hypotension and bradycardia. In spite of these phenotypes, analysis of heart rate variability and serum catecholamine levels revealed that sympathetic activity is upregulated in Nrd1-/- mice. Furthermore, Nrd1-/- mice showed abnormal sympathetic innervation patterning. Pharmacological blocking of autonomic nervous system showed that the intrinsic heart rate of Nrd1-/- mice was significantly decreased. In conclusion, NRDc critically regulates circulatory dynamics through modulating intrinsic heart rate and cardiac sympathetic innervation.
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Report
(4 results)
Research Products
(66 results)
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[Journal Article] Critical roles of nardilysin in the maintenance of body temperature homeostasis2014
Author(s)
Hiraoka Y, Matsuoka T, Ohno M, Nakamura K, Saijo S, Matsumura S, Nishi K, Sakamoto J, Chen Po-Min, Inoue K, Fushiki T, Kita T, Kimura T and Nishi E
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Journal Title
Nat. Commun
Volume: 5
Issue: 1
Pages: 3224-3224
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Nardilysin prevents amyloid plaque formation by enhancing a-secretase activity in an Alzheimer's disease mouse model2014
Author(s)
Ohno M, Hiraoka Y, Lichtenthaler S, Nishi K, Saijo S, Matsuoka T, Tomimoto H, Araki W, Takahashi R, Kita T, Kimura T and Nishi E
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Journal Title
Neurobiol Aging
Volume: 35
Issue: 1
Pages: 213-22
DOI
Related Report
Peer Reviewed / Open Access
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[Presentation] Nardilysin Regulates Adaptive Thermogenesis and Body Temperature Homeostasis through Modulation of PGC-1α2014
Author(s)
Saijo S, Hiraoka Y, Matsuoka T, Ohno M, Nakamura K, Matsumura S, Nishi K, Sakamoto J, Chen P, Kita T, Kimura T, Nishi E
Organizer
第78回日本循環器学会総会
Place of Presentation
東京
Year and Date
2014-03-23
Related Report
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[Presentation] Nardylisin controls glucose metabolism through the regulation of insulin secretion2014
Author(s)
Nishi K, Sato Y, Ohno M, Hiraoka Y, Saijyo S, Sakamoto J, Chen P, Kita T, Inagaki N, Kimura T, Nishi E
Organizer
第78回日本循環器学会学術集会
Place of Presentation
東京
Year and Date
2014-03-21
Related Report
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[Presentation] Nardilysin Regulates Adaptive Thermogenesis and Body Temperature Homeostasis through Modulation of PGC-1α2014
Author(s)
Saijo S, Hiraoka Y, Matsuoka T, Ohno M, Nakamura K, Matsumura S, Nishi K, Sakamoto J, Chen P, Kita T, Kimura T, Nishi E.
Organizer
第78回日本循環器学会学術集会
Place of Presentation
東京
Related Report
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[Presentation] Nardilysin, an Activator of Ectodomain Shedding, is a Novel and Potent Biomarker for Acute Coronary Syndrome(English session 最優秀賞)2013
Author(s)
Ohno M, Watanabe S, Hiraoka Y, Nishi K, Saijo S, Sakamoto J, Chen PM, Kita T, Nishi E, Kimura T
Organizer
第115回日本循環器学会近畿地方会
Place of Presentation
京都
Year and Date
2013-06-15
Related Report
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[Presentation] ナルディライジンは PGC-1αを制御することで体温恒常性維持機構と適応熱産生を調節する2013
Author(s)
西城さやか, 平岡 義範, 松岡 龍彦, 大野美紀子,中村 和弘, 松村 成暢, 西 清人, 坂本二郎, 陳 博敏, 北 徹, 木村 剛, 西英一郎
Organizer
第36回日本分子生物学会年会
Place of Presentation
神戸
Related Report
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[Presentation] ナルディラインジンはグルコース応答性インスリン分泌を制御する2013
Author(s)
西 清人, 佐藤 雄一, 大野 美紀子, 平岡 義範, 西城 さやか, 坂本 二郎, 陳 博敏, 松岡龍彦, 北 徹, 稲垣 暢也, 木村 剛, 西 英一郎
Organizer
第36回日本分子生物学会年会
Place of Presentation
神戸
Related Report
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[Presentation] Nardilysin is a critical regulator of insulin secretion and glucose metabolism |2013
Author(s)
Nishi K, Sato Y, Ohno M, Hiraoka Y, Saijyo S, Sakamoto J, Chen P, Kita T, Inagaki N, Kimura T, Nishi E
Organizer
American Heart Association scientific sessions 2013
Place of Presentation
Dallas, USA
Related Report
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[Presentation] 体温恒常性維持におけるナルディライジンの役割2013
Author(s)
西城さやか, 平岡 義範, 松岡 龍彦, 大野美紀子, 中村 和弘, 松村 成暢, 西 清人, 坂本二郎, 陳 博敏, 北 徹, 木村 剛, 西 英一郎
Organizer
平成 25年度 温熱生理研究会
Place of Presentation
岡崎
Related Report
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[Presentation] ナルディライジンによる心拍数制御機構(学会奨励賞受賞)2013
Author(s)
大野美紀子, 平岡義範, 松浦博, 西清人, 西城さやか, 坂本二郎, 陳博敏, 牧山武, 北徹, 木村剛, 西英一郎
Organizer
第18回日本病態プロテアーゼ学会学術集会
Place of Presentation
大阪
Related Report
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[Presentation] Nardilysin, an Activator of Ectodomain Shedding, is a Novel and Potent Biomarker for Acute Coronary Syndrome(口頭)2013
Author(s)
Ohno M, Watanabe S, Hiraoka Y, Matsuoka T, Nishi K, Saijo S, Sakamoto J, Chen PM, Inoue K, Kita T, Kimura T, Nishi E
Organizer
第77回日本循環器学会総会
Place of Presentation
横浜
Related Report
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[Presentation] Nardilysin is a critical regulator of insulin secretion and glucose metabolism2013
Author(s)
Nishi K, Sato Y, Ohno M, Hiraoka Y, Saijyo S, Sakamoto J, Chen P, Kita T, Inagaki N, Kimura T, Nishi E.
Organizer
American Heart Association scientific sessions 2013
Place of Presentation
Dallas, USA
Related Report
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[Presentation] 体温恒常性維持におけるナルディライジンの役割2013
Author(s)
西城さやか,平岡 義範,松岡 龍彦,大野 美紀子,中村 和弘,松村 成暢,西 清人,坂本 二郎,陳 博敏, 北 徹,木村 剛,西 英一郎
Organizer
温熱生理研究会
Place of Presentation
岡崎
Related Report
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[Presentation] ナルディライジンはPGC-1αを制御することで体温恒常性維持機構と適応熱産生を調節する2013
Author(s)
西城さやか,平岡 義範,松岡 龍彦,大野 美紀子,中村 和弘,松村 成暢,西 清人,坂本 二郎,陳 博敏, 北 徹,木村 剛,西 英一郎
Organizer
第36回日本分子生物学会年会
Place of Presentation
神戸
Related Report
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[Presentation] Nardilysin, an Activator of Ectodomain Shedding, is a Novel and Potent Biomarker for Acute Coronary Syndrome2013
Author(s)
Ohno M, Watanabe S, Hiraoka Y, Matsuoka T, Nishi K, Saijo S, Sakamoto J, Chen PM, Inoue K, Kita T, Kimura T, Nishi E.
Organizer
第77回日本循環器学会総会
Place of Presentation
横浜
Related Report
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[Presentation] NRDc regulates circulatory dynamics through modulating sinus node automaticity and cardiac sympathetic innervation2012
Author(s)
Ohno M, Hiraoka Y, Matsuura H, Matsuoka T, Nishi K, Saijo S, Sakamoto J, Chen PM, Kita T, Kimura T, Nishi E
Organizer
Neuro-Vascular Wiring Symposium 2012
Place of Presentation
Nara
Related Report
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[Presentation] Nardilysin, an activator of ectodomain shedding, is a novel and potent biomarker for acute coronary syndrome口頭発表2012
Author(s)
Ohno M, Watanabe S, Hiraoka Y, Matsuoka T, Nishi K, Saijo S, Kita T, Nishi E, Kimura T
Organizer
ESC Congress 2012
Place of Presentation
Munich Germany
Related Report
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[Presentation] Nardilysin, an activator of ectodomain shedding, is a novel and potent biomarker for acute coronary syndrome2012
Author(s)
Ohno M, Watanabe S, Hiraoka Y, Matsuoka T, Nishi K, Saijo S, Kita T, Nishi E, Kimura T.
Organizer
European Society of Cardiology, Congress 2012
Place of Presentation
Munich- Germany
Related Report
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[Presentation] NRDc regulates circulatory dynamics through modulating sinus node automaticity and cardiac sympathetic innervation2012
Author(s)
Ohno M, Hiraoka Y, Matsuura H, Matsuoka T, Nishi K, Saijo S, Sakamoto J, Chen PM, Kita T, Kimura T, Nishi E.
Organizer
Neuro-Vascular Wiring Symposium 2012
Place of Presentation
奈良
Related Report
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[Presentation] Nardilysin, an Activator of Ectodomain Shedding, is a Novel and Potent Biomarker for Acute Coronary Syndrome
Author(s)
Ohno M, Watanabe S, Hiraoka Y, Nishi K, Saijo S, Sakamoto J, Chen PM, Kita T, Nishi E, Kimura T.
Organizer
第115回日本循環器学会近畿地方会
Place of Presentation
京都
Related Report
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