Basic research for the development of innovative therapeutic approaches against heart failure
| Project/Area Number |
18H02809
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (B)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Review Section |
Basic Section 53020:Cardiology-related
|
|---|
| Research Institution | Kumamoto University |
|---|
Principal Investigator |
OIKE Yuichi 熊本大学, 大学院生命科学研究部(医), 教授 (90312321)
|
|---|
| Project Period (FY) |
2018-04-01 – 2021-03-31
|
| Project Status |
Completed (Fiscal Year 2020)
|
| Budget Amount *help |
¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000)
Fiscal Year 2020: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2019: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
Fiscal Year 2018: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
|
|---|
| Keywords | 心不全 / ミトコンドリア / エネルギー代謝 / ANGPTL2 / 心筋 |
|---|
| Outline of Final Research Achievements |
In this study, we showed a molecular mechanism underlying the enhancement of mitochondrial energy metabolism in cardiomyocytes by ANGPTL2 suppression. Suppressing ANGPTL2 expression in cardiomyocytes enhances mitochondrial respiratory function by increasing the respiratory chain complex II and decreases the production of reactive oxygen species. Moreover, we identified a novel lncRNA Caren and demonstrated that Caren functions in cardioprotection by enhancing mitochondrial biogenesis and inhibiting the activation of DNA damage response in cardiomyocytes. We also found that the expression level of Caren decreases in cardiomyocytes of failing heart and showed that re-expression of Caren in cardiomyocytes could be a novel therapeutic strategy against heart failure.
|
| Academic Significance and Societal Importance of the Research Achievements |
本研究の成果として、心筋細胞におけるミトコンドリアエネルギー代謝機能の改善が、心不全の新たな治療戦略として有効であることを明らかにするなど、新規治療法開発につながる重要な基盤研究となった。さらに、本研究の成果は、心筋細胞におけるミトコンドリアエネルギー代謝機能制御機構として、ANGPTL2抑制による呼吸鎖複合体IIの活性促進や新規lncRNAであるCarenによるミトコンドリア生合成促進などの作用機序の解明といった学術的意義も有する。
|
Report
(4 results)
Research Products
(43 results)
-
[Journal Article] The lncRNA Caren antagonizes heart failure by inactivating DNA damage response and activating mitochondrial biogenesis.2021
Author(s)
Sato M, Kadomatsu T, Miyata K, Warren SJ, Tian Z, Zhu S, Horiguchi H, Makaju A, Bakhtina A, Morinaga J, Sugizaki T, Hirashima K, Yoshinobu K, Imasaka M, Araki M, Komohara Y, Wakayama T, Nakagawa S, Franklin S, Node K, Araki K, Oike Y.
-
Journal Title
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
-
-
[Journal Article] Tumor cell-derived angiopoietin-like protein 2 establishes a preference for glycolytic metabolism in lung cancer cells.2020
Author(s)
Osumi H, Horiguchi H, Kadomatsu T, Tashiro K, Morinaga J, Takahashi T, Ikeda K, Ito T, Suzuki M, Endo M, Oike Y
-
Journal Title
Cancer Sci
Volume: -
Issue: 4
Pages: 1241-1253
DOI
Related Report
Peer Reviewed / Open Access
-
[Journal Article] Circulating angiopoietin-like protein 2 levels and arterial stiffness in patients receiving maintenance hemodialysis: A cross-sectional study.2020
Author(s)
Fukami H, Morinaga J, Okadome Y, Nishiguchi Y, Iwata Y, Kanki T, Nakagawa T, Izumi Y, Kakizoe Y, Kuwabara T, Horiguchi H, Sato M, Kadomatsu T, Miyata K, Tajiri T, Oike Y, Mukoyama M.
-
Journal Title
Atherosclerosis.
Volume: 315
Pages: 18-23
DOI
Related Report
Peer Reviewed / Open Access
-
[Journal Article] Loss of Endogenous HMGB2 Promotes Cardiac Dysfunction and Pressure Overload-Induced Heart Failure in Mice2019
Author(s)
Sato M, Miyata K, Tian Z, Kadomatsu T, Ujihara Y, Morinaga J, Horiguchi H, Endo M, Zhao J, Zhu S, Sugizaki T, Igata K, Muramatsu M, Minami T, Ito T, Bianchi ME, Mohri S, Araki K, Node K, Oike Y
-
Journal Title
Circulation Journal
Volume: 83
Issue: 2
Pages: 368-378
DOI
NAID
ISSN
1346-9843, 1347-4820
Year and Date
2019-01-25
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
-
[Journal Article] Dual functions of angiopoietin-like protein 2 signaling in tumor progression and anti-tumor immunity.2019
Author(s)
Horiguchi H, Kadomatsu T, Kurahashi R, Hara C, Miyata K, Baba M, Osumi H, Terada K, Araki K, Takai T, Kamba T, Linehan WM, Moroishi T & Oike Y.
-
Journal Title
Genes Dev
Volume: 33
Pages: 1641-1656
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
-
-
[Journal Article] Circulating angiopoietin-like protein 2 levels and mortality risk in patients receiving maintenance hemodialysis: a prospective cohort study2019
Author(s)
Morinaga J, Kakuma T, Fukami H, Hayata M, Uchimura K, Mizumoto T, Kakizoe Y, Miyoshi T, Shiraishi N, Adachi M, Izumi Y, Kuwabara T, Okadome Y, Sato M, Horiguchi H, Sugizaki T, Kadomatsu T, Miyata K, Tajiri S, Tajiri T, Tomita K, Kitamura K, Oike Y, Mukoyama M.
-
Journal Title
Nephrology Dialysis Transplantation
Volume: 印刷中
Issue: 5
Pages: 854-860
DOI
Related Report
Peer Reviewed / Open Access
-
[Journal Article] TFE3 Xp11.2 translocation renal cell carcinoma mouse model reveals novel therapeutic targets and identifies GPNMB as a diagnostic marker for human disease.2019
Author(s)
Baba M, Furuya M, Motoshima T, Lang M, Funasaki S, Ma W, Sun HW, Hasumi H, Huang Y, Kato I, Kadomatsu T, Satou Y, Morris N, Karim BO, Ileva L, Kalen JD, Wilan Krisna LA, Hasumi Y, Sugiyama A, Kurahashi R, Nishimoto K, Oyama M, Nagashima Y, Kuroda N, Araki K, Eto M, Yao M, Kamba T, Suda T, Oike Y, Schmidt LS, Linehan WM
-
Journal Title
Molecular Cancer Research
Volume: 印刷中
Issue: 8
Pages: 1613-1626
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
-
[Journal Article] MiR-204-5p: a novel candidate urinary biomarker of Xp11.2 translocation renal cell carcinoma.2019
Author(s)
Kurahashi R, Kadomatsu T, Baba M, Hara C, Itoh H, Miyata K, Endo M, Morinaga J, Terada K, Araki K, Eto M, Schmidt LS, Kamba T, Linehan WM, Oike Y.
-
Journal Title
Cancer Science
Volume: 印刷中
Issue: 6
Pages: 1897-1908
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
