Inositol 1,4,5- trisphosphate receptor 2 as a novel pulmonary artery smooth muscle marker to delineate the processes of cardiopulmonary development

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K17309
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 52050:Embryonic medicine and pediatrics-related
• Research Institution: Keio University
• Principal Investigator: ISHIZAKI Reina 慶應義塾大学, 医学部(信濃町), 助教 (70528299)
• Project Period (FY): 2019-04-01 – 2021-03-31
• Keywords: IP3R2 / 肺動脈平滑筋 / 発生 / 総動脈幹症 / Tbx1

Outline of Final Research Achievements

Severe congenital heart diseases are often complicated by pulmonary artery anomalies, which are difficult to treat. The pathogenesis of pulmonary artery anomalies remains unclear, and analysis using molecular markers specific for pulmonary artery development is required.
In this study, we elucidated that inositol triphosphate receptor type 2 (IP3R2) is expressed in pulmonary artery smooth muscle, and by using IP3R2 as a pulmonary artery smooth muscle-specific molecular marker, we succeeded in visualizing the developmental process of pulmonary arteries in mice. As a result, it was clarified that pulmonary artery smooth muscle develops from the cardiac outflow tract toward the periphery of pulmonary arteries. We also applied this technique to the analysis of a mouse model of truncus arteriosus, and showed the mechanism by which truncus arteriosus develops due to the absence or hypoplasia of the base of the pulmonary arterial trunk.

Free Research Field

心臓発生

Academic Significance and Societal Importance of the Research Achievements

本研究は、これまでに存在しなかった肺動脈の発生を可視化することができる有用なIP3R2-LacZマウスという実験動物を確立した。さらに、IP3R2-LacZマウスを用いて、総動脈幹症という重症先天性心疾患の発症機序とそれに伴う肺動脈の形態異常の解明に応用することができた。先天性心疾患の診療を向上させるために、病態解明と予防・再生医療に発展する基礎研究は重要であり、今回確立したIP3R2-LacZマウスは様々な先天性心疾患と合併する肺動脈異常の病態解明に応用できる可能性がある。