Pathophysiology of left ventricular noncompaction: focus on the importance of the downstream pathway of the transcription factor TBX5
Project/Area Number |
19K08295
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Review Section |
Basic Section 52050:Embryonic medicine and pediatrics-related
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Research Institution | University of Toyama |
Principal Investigator |
Hirono Keiichi 富山大学, 学術研究部医学系, 講師 (80456384)
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Co-Investigator(Kenkyū-buntansha) |
森 寿 富山大学, 学術研究部医学系, 教授 (00239617)
長谷川 英之 富山大学, 学術研究部工学系, 教授 (00344698)
高崎 一朗 富山大学, 学術研究部工学系, 准教授 (00397176)
西田 尚樹 富山大学, 学術研究部医学系, 教授 (10315088)
伊吹 圭二郎 富山大学, 学術研究部医学系, 助教 (20566096)
市田 蕗子 富山大学, 事務局, 学長補佐 (30223100)
畑 由紀子 富山大学, 学術研究部医学系, 准教授 (30311674)
小澤 綾佳 富山大学, 学術研究部医学系, 助教 (40596540)
長岡 亮 富山大学, 学術研究部工学系, 准教授 (60781648)
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Project Period (FY) |
2019-04-01 – 2022-03-31
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Project Status |
Completed (Fiscal Year 2021)
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Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2021: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2020: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2019: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
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Keywords | 心筋症 / 心筋緻密化障害 |
Outline of Research at the Start |
心筋緻密化障害は、心室壁の過剰な網目状の肉柱形成と深い間隙を特徴とする心筋症である。しかしながら、病態の多くが不明であり、根本的な原因究明が急務である。今回の我々の目的は、TBX5 遺伝子の一塩基変異を起点に分化・成熟過程に関連する分子が次々と障害され心筋緻密化障害が起こるという仮定に基づき心筋緻密化障害の病態とTBX5の新たな機能を解明することである。TBX5 遺伝子の一塩基変異による機能障害を検証するために、TBX5のレポーターアッセイ、患者由来iPS細胞の発現プロファイル解析によりTBX5の下流経路の障害を検証する。
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Outline of Final Research Achievements |
Left ventricular noncompactio is a cardiomyopathy characterized morphologically by excessive reticular column formation and deep gaps in the ventricular wall, much of the pathogenesis of which is unknown. We tested the hypothesis that TBX5 gene mutations in the non-T-box domain region cause cardiac densification defects as a result of sequential changes in gene expression profiles associated with differentiation and maturation processes during myocardial development, with associated protein increases and decreases. This study allowed us to elucidate the pathways through the T-box and non-T-box domains of TBX5 and the interrelationship between the two. In short, we were able to identify a new role for the TBX5 gene in relation to differentiation and maturation processes during myocardial development.
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Academic Significance and Societal Importance of the Research Achievements |
TBX5遺伝子の心筋の発生段階における分化・成熟過程に関連する新たな役割を明らかにすることができた。また、遺伝子変異に起因する疾患発症機序の解明に向けた分子遺伝学的アプローチの手法が確立できた。
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Report
(4 results)
Research Products
(46 results)
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[Journal Article] Electrocardiographic Diagnosis of Hypertrophic Cardiomyopathy in the Pre- and Post-Diagnostic Phases in Children and Adolescents2021
Author(s)
Yoshinaga M, Horigome H, Yasuda K, Kogaki S, Tateno S, Ohta K, Hirono K, Hosokawa S, Takechi F, Ishikawa Y, Hata T, Ichida F, Ohno S, Makita N, Horie M, Takahashi H, Nagashima M.
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Journal Title
Circulation Journal
Volume: 86
Issue: 1
Pages: 118-127
DOI
NAID
ISSN
1346-9843, 1347-4820
Year and Date
2021-12-24
Related Report
Peer Reviewed / Open Access
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[Journal Article] Poor Myocardial Compaction in a Patient with Recessive <i>MYL2</i> Myopathy2021
Author(s)
Tamamitsu AM, Nakagama Y, Domoto Y, Yoshida K, Ogawa S, Hirono K, Shindo T, Ogawa Y, Nakano K, Asakai H, Hirata Y, Matsui H, Inuzuka R
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Journal Title
International Heart Journal
Volume: 62
Issue: 2
Pages: 445-447
DOI
NAID
ISSN
1349-2365, 1349-3299
Year and Date
2021-03-30
Related Report
Peer Reviewed / Open Access
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[Journal Article] Incidence and Expected Probability of Liver Cirrhosis and Hepatocellular Carcinoma After Fontan Operation.2021
Author(s)
Nii M, Inuzuka R, Inai K, Shimada E, Shinohara T, Kogiso T, Ono H, Ootsuki S, Kurita Y, Takeda A, Hirono K, Takei K, Yasukochi S, Yoshikawa T, Furutani Y, Shinozaki T, Matsuyama Y, Senzaki H, Tokushige K, Nakanishi T.
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Journal Title
Circulation
Volume: 144
Issue: 25
Pages: 2043-2045
DOI
Related Report
Peer Reviewed
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[Journal Article] Anatomical Classification and Posttreatment Remodeling Characteristics to Guide Management and Follow-Up of Neonates and Infants With Coronary Artery Fistula: A Multicenter Study From the Coronary Artery Fistula Registry.2021
Author(s)
Gowda ST, Latson L, Sivakumar K, Hiremath G, Crystal M, Law M, Shahanavaz S, Asnes J, Veeram Reddy S, Kobayashi D, Alwi M, Ichida F, Hirono K, Tahara M, Takeda A, Minami T, Kutty S, Nugent AW, Forbes T, Prieto LR, Qureshi AM.
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Journal Title
Circ Cardiovasc Interv.
Volume: 14
Issue: 12
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Predictors of long-term mortality among perioperative survivors of Fontan operation.2021
Author(s)
Inai K, Inuzuka R, Ono H, Nii M, Ohtsuki S, Kurita Y, Takeda A, Hirono K, Takei K, Yasukouchi S, Yoshikawa T, Furutani Y, Shimada E, Shinohara T, Shinozaki T, Matsuyama Y, Senzaki H, Nakanishi T.
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Journal Title
Eur Heart J
Volume: -
Issue: 25
Pages: 2373-2384
DOI
Related Report
Peer Reviewed
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[Journal Article] The mid-term outcome of interventricular septal hematoma after ventricular septal defect closure. Aoki M, Ikeno Y, Ibuki K, Ozawa S, Hirono K, Yoshimura N.2021
Author(s)
Aoki M, Ikeno Y, Ibuki K, Ozawa S, Hirono K, Yoshimura N.
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Journal Title
Asian Cardiovasc Thorac Ann.
Volume: -
Issue: 7
Pages: 840-843
DOI
Related Report
Peer Reviewed
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[Journal Article] Outcomes of hypertrophic cardiomyopathy in Japanese children: a retrospective cohort study.2021
Author(s)
Mori H, Yoshikawa T, Kimura H, Ono H, Kato H, Ono Y, Nii M, Shindo T, Inuzuka R, Horigome H, Miura M, Hirono K, Kobayashi T, Kogaki S, Furutani Y, Nakanishi T
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Journal Title
Heart Vessels.
Volume: -
Issue: 6
Pages: 109-11
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Reversible left ventricular noncompaction caused by hypertensive hydrocephalus: a pediatric case report.2021
Author(s)
ato R, Taneichi H, Takarada S, Okabe M, Miyao N, Nakaoka H, Ibuki K, Ozawa S, Adachi Y, Yoshimura N, Saito K, Ichida F, Hirono K.
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Journal Title
BMC Pediatr.
Volume: 21
Issue: 1
Pages: 205-205
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] The combination of the neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios as a novel predictor of intravenous immunoglobulin resistance in patients with Kawasaki disease: a multicenter study.2020
Author(s)
Kanai T, Takeshita S, Kawamura Y, Kinoshita K, Nakatani K, Iwashima S, Takizawa Y, Hirono K, Mori K, Yoshida Y, Nonoyama S.
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Journal Title
Heart Vessels.
Volume: 35
Issue: 10
Pages: 1463-1472
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] TBX5 R264K acts as a modifier to develop dilated cardiomyopathy in mice independently of T-box pathway2020
Author(s)
Miyao N., Hata Y., Izumi H., Nagaoka R., Oku Y., Takasaki I., Ishikawa T., Takarada S., Okabe M., Nakaoka H., Ibuki K., Ozawa S., Yoshida T., Hasegawa H., Makita N., Nishida N., Mori H., Ichida F., Hirono K.
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Journal Title
PLOS ONE
Volume: 15
Issue: 4
Pages: 0227393-0227393
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] CYP2C9, VKORC1, and CYP4F2 Polymorphisms and Pediatric Warfarin Maintenance Dose: A Systematic Review and Meta-Analysis2020
Author(s)
Takeuchi M, Kobayashi T, Biss T, Kamali F, Vear SI, Ho RH, Bajolle F, Loriot MA, Shaw K, Carleton BC, Hamberg AK, Wadelius M, Hirono K, Taguchi M, Wakamiya T, Yanagimachi M, Hirai K, Itoh K, Brandão LR, and Ito S.
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Journal Title
Pharmacogenomics J
Volume: 20
Issue: 2
Pages: 306-319
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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[Journal Article] Left Ventricular Noncompaction and Congenital Heart Disease Increases the Risk of Congestive Heart Failure.2020
Author(s)
Hirono K, Hata Y, Miyao N, Okabe M, Takarada S, Nakaoka H, Ibuki K, Ozawa S, Yoshimura N, Nishida N, Ichida F, Lvnc Study Collaborators.
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Journal Title
J Clin Med.
Volume: 9
Issue: 3
Pages: 785-785
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Lipidomics links oxidized phosphatidylcholines and coronary arteritis in Kawasaki disease2019
Author(s)
Nakashima Y, Sakai Y, Mizuno Y, Furuno K, Hirono K, Takatsuki S, Suzuki H, Onouchi Y, Kobayashi T, Tanabe K, Hamase K, Miyamoto T, Aoyagi R, Arita M, Yamamura K, Tanaka T, Nishio H, Takada H, Ohga S, Hara T.
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Journal Title
Cardiovascular Research
Volume: -
Issue: 1
Pages: 0-0
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Efficacy of primary treatment with immunoglobulin plus ciclosporin for prevention of coronary artery abnormalities in patients with Kawasaki disease predicted to be at increased risk of non-response to intravenous immunoglobulin (KAICA): a randomised controlled, open-label, blinded-endpoints, phase 3 trial2019
Author(s)
Hamada H, Suzuki H, Onouchi Y, Ebata R, Terai M, Fuse S, Okajima Y, Kurotobi S, Hirai K, Soga T, Ishiguchi Y, et al.
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Journal Title
Lancet.
Volume: 393(10176):
Issue: 10176
Pages: 1128-1137
DOI
Related Report
Peer Reviewed / Open Access
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[Presentation] Genotype-Phenotype correlation for children with left ventricular noncompaction and congenital heart disease2021
Author(s)
Keiichi Hirono, Yukiko Hata, Nariaki Miyao, Mako Okabe, Shinya Takarada, Hideyuki Nakaoka, Keijiro Ibuki, Sayaka Ozawa, Naoki Yoshimura, Naoki Nishida, Fukiko Ichida, and LVNC study collaborators
Organizer
第85回日本循環器学会
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