Development of novel diagnostic and therapeutic methods for cardiac diseases based on the elucidation of the regulatory mechanism of glycosylation of proBNP
Project/Area Number |
19K08580
|
Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Multi-year Fund |
Section | 一般 |
Review Section |
Basic Section 53020:Cardiology-related
|
Research Institution | Kyoto University |
Principal Investigator |
|
Co-Investigator(Kenkyū-buntansha) |
桑原 宏一郎 信州大学, 学術研究院医学系, 教授 (30402887)
錦見 俊雄 京都大学, 医学研究科, 非常勤講師 (80291946)
|
Project Period (FY) |
2019-04-01 – 2022-03-31
|
Project Status |
Completed (Fiscal Year 2021)
|
Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2021: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
|
Keywords | proBNP / 糖鎖修飾 / 糖鎖 / ナトリウム利尿ペプチド |
Outline of Research at the Start |
本申請研究では、脳性ナトリウム利尿ペプチドBNPの前駆体proBNP分泌に関わる糖鎖修飾機序に基づく心疾患の新たな診断法、治療法の開発を目的とする。即ち、本研究では①心疾患の種々の病態・病期におけるproBNPの糖鎖構造の相違を明らかにすることにより、糖鎖構造に基づいた、既存の診断法にない、より詳細な心筋の病態を評価しうる新たな診断法の開発を目指す、②不全心筋において生理活性の極めて弱いproBNPが分泌増加するが、proBNPから生理活性の強いBNP1-32への生体内での生成を促進することによる心疾患の新たな治療法の開発に向けた基盤的な研究を行う。
|
Outline of Final Research Achievements |
BNP is a cardioprotective peptide secreted from the heart. We have reported that the precursor proBNP, which is much less bioactive than BNP, exists in the blood and that glycosylation of proBNP is involved in its secretion mechanism. In this study, we attempted to analyze glycan structures to create a new diagnostic method by elucidating glycan structures. It became clear the possibility that the glycan structures may be diverse in proBNP produced in non-cardiac myocytes, and we will continue to analyze them in more physiological situations from cardiac myocytes. On the other hand, the involvement of molecules other than miR30 and GALNT in glycosylation and the possibility that the molecules involved may change depending on the pathological condition were found, and we will continue further research in order to create new treatment methods.
|
Academic Significance and Societal Importance of the Research Achievements |
本研究により、低活性のproBNP分泌メカニズムの一端が明らかとなり、これらの分子メカニズムを修飾することで、心不全の新たな診断法や、活性の強いBNPの分泌が促進されるような新たな心不全治療の開発につながる可能性が有る意義のある研究成果が得られたと考える。
|
Report
(4 results)
Research Products
(49 results)
-
-
[Journal Article] Overview of the 84<sup>th</sup> Annual Scientific Meeting of the Japanese Circulation Society ― Change Practice! ―2021
Author(s)
Koh Ono, Satoshi Shizuta, Erika Yamamoto, Naritatsu Saito, Neiko Ozasa, Takao Kato, Eri Kato, Takahiro Horie, Junichi Tazaki, Hiroki Shiomi, Shin Watanabe, Hirotoshi Watanabe, Yugo Yamashita, Yusuke Yoshikawa, Hideyuki Kinoshita, Takeru Makiyama, Yoshinori Yoshida, Noboru Ashida, Yasuaki Nakagawa, et al.
-
Journal Title
Circulation Journal
Volume: 85
Issue: 3
Pages: 323-329
DOI
NAID
ISSN
1346-9843, 1347-4820
Year and Date
2021-02-25
Related Report
Peer Reviewed
-
-
[Journal Article] Molecular ration of mature B-type natriuretic peptide in acute heart failure: an indicator for ventricular contractile recovery.2021
Author(s)
Kimura A, Takahama H, Nishikimi T, Takashio S, Hayashi T, Nagai-Okatani C, Nakagawa Y, Yasuda S, Anzai T, Minamino N, Izumi C.
-
Journal Title
ESC heart failure
Volume: 8
Issue: 4
Pages: 5617-5621
DOI
Related Report
Peer Reviewed
-
-
[Journal Article] Rationale and design of the EMPEREAN study2020
Author(s)
Motoki H, Masuda I, Yasuno S, Oba K, Shoin W, Usami S, Saito Y, Waki M, Komatsu M, Ueshima K, Nakagawa Y, Son C, Yonemitsu S, Hiramitsu S, Konda M, Onishi K, Kuwahara K.
-
Journal Title
ESC heart Fail.
Volume: 7
Issue: 5
Pages: 3134-3141
DOI
Related Report
Peer Reviewed / Open Access
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
[Presentation] 末梢性肺動脈狭窄症に冠動脈肺動脈瘻を合併した1症例2021
Author(s)
堀晃暢, 鮑炳元, 木下秀之, 伊藤大樹, 中井久登, 柳澤洋, 稲住英明, 渡邉真, 田崎淳一, 堀江貴裕, 中川靖章, 尾野亘, 木村剛
Organizer
第131回日本循環器学会 近畿地方会
Related Report
-
-
-
-
-
-
-
-
-
-
-
-
-
[Presentation] Increased Gao expression underlies cardiac dysfunction and lethal arrhythmias accompanied with abnormal Ca2+ handling.2019
Author(s)
Inazumi H, Kuwahara K, Kuwabara Y, Nakagawa Y, Kinoshita H, Moriuchi K, Yanagisawa H, Nishikimi T, Oya M, Yamada M, Kashihara T, Kurebayashi N, Sugihara M, Nakao K, Kimura T.
Organizer
European Society of Cardiology2019
Related Report
Int'l Joint Research
-
-
-
-
-
-
-
-
-
-
[Presentation] Increased expression of Gαo plays a pivotal role in the progression of heart failure by impairing Ca2+ homeostasis2019
Author(s)
H Inazumi, K Kuwahara, Y Kuwabara, Y Nakagawa, H Kinoshita, K Moriuchi, H Yanagisawa , T Nishikimi , M Oya, M Yamada, T Kashihara, N Kurebayashi, M Sugihara, K Nakao, T Kimura
Organizer
第36回国際心臓研究学会日本部会
Related Report
-
-