Pathological functions of cardiac fibroblasts in pediatric cardiomyopathy

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K07789
• 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: Osaka University
• Principal Investigator: ISHII RYO 大阪大学, 医学系研究科, 助教 (90794008)
• Co-Investigator(Kenkyū-buntansha): 石田 秀和 大阪大学, 医学系研究科, 助教 (50467552) ; 小垣 滋豊 大阪大学, 医学系研究科, 招へい教員 (00311754)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 心筋症 / 心筋線維芽細胞 / 心筋細胞 / 遺伝子発現解析 / 心臓移植

Outline of Final Research Achievements

The precise molecular mechanisms of idiopathic cardiomyopathy is still unknown. We performed whole exome analysis for Japanese pediatric cardiomyopathy patients and identified lots of gene mutations which cause cardiomyopathy in children. We cultured cardiac fibroblasts obtained from the various cardiomyopathy patients while the heart transplantation or ventricular assist device implantation. The diseased cardiac fibroblasts show significant different gene expression patterns as compared to the healthy cardiac fibroblasts. When we co-cultured the healthy cardiomyocytes with diseased cardiac fibroblasts, the cardiomyocytes showed weaken contraction and dilatation ability. We established induced pluripotent stem cell lines from the patients with idiopathic cardiomyopathy in children.

Free Research Field

小児循環器学

Academic Significance and Societal Importance of the Research Achievements

今回の私達の研究により、これまで心筋細胞にのみ原因があると考えられてきた特発性心筋症の病態において、心筋線維芽細胞が重要な役割を果たしていることが明らかとなった。心筋症の患者から得られた心筋線維芽細胞が、健常な心筋細胞の収縮能や拡張能に悪影響を与えているということは大きな発見である。今後、心筋細胞だけでなく心筋線維芽細胞もターゲットとした新しい治療法の開発につながる可能性がある。