Pathophysiology of left ventricular noncompaction: focus on the importance of the downstream pathway of the transcription factor TBX5

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K08295
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 52050:Embryonic medicine and pediatrics-related
• Research Institution: University of Toyama
• Principal Investigator: Hirono Keiichi 富山大学, 学術研究部医学系, 講師 (80456384)
• 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)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 心筋症

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.

Free Research Field

小児循環器

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。