2022 Fiscal Year Final Research Report
Reparative macrophages contribute to development of solid replacement fibrosis through protecting cardiac fibroblasts
| Project/Area Number |
20K09153
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 55030:Cardiovascular surgery-related
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| Research Institution | Jichi Medical University |
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Principal Investigator |
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| Project Period (FY) |
2020-04-01 – 2023-03-31
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| Keywords | 心筋梗塞 / 線維化 / マクロファージ / 線維芽細胞 |
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| Outline of Final Research Achievements |
Because the mechanism by which post-MI cardiac fibrosis is regulated is not fully understood, we investigated the cellular and molecular mechanisms of post-MI fibrotic tissue formation. CD206+F4/80+CD11b+ M2-like macrophages collected from mouse hearts on post-MI day 7 showed increased expression of neuregulin 1 (Nrg1). Nrg1/ErbB/PI3K/Akt signaling was activated in damaged cardiac fibroblasts. Interestingly, systemic blockade of ErbB function in MI model mice exacerbated inflammation.The molecular mechanism underlying regulation of fibrotic tissue formation in the infarcted myocardium was shown in part to be attenuation of apoptosis and senescence of cardiac fibroblasts by activation of Nrg1/ErbB/PI3K/Akt signaling. M2-like macrophage-mediated regulation of Nrg1/ErbB signaling has a substantial effect on fibrotic tissue formation in the infarcted adult mouse heart and is critical for suppressing the progression of senescence and apoptosis of cardiac fibroblasts.
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| Free Research Field |
心臓血管外科
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| Academic Significance and Societal Importance of the Research Achievements |
本研究では虚血障害による線維芽細胞の老化やアポトーシスを制御する分子としてマクロファージが分泌するNeuregulin 1 (Nrg1)を同定した。慢性心不全の病態に対する心臓線維芽細胞の異常性の果たす重要な役割を考慮すると、梗塞時にダメージを受けた線維芽細胞の長期的予後に対する影響も少なく無いことが予想される。Neuregulin 1による細胞老化やアポトーシスの制御機構の一端が本研究で明らかとなり、今後心不全予後に対する新たな戦略に繋がる可能性がある
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