TY - JOUR T1 - Reparative macrophages regulate fibrosis by attenuating apoptosis and senescence of fibroblasts JF - bioRxiv DO - 10.1101/2021.01.29.428912 SP - 2021.01.29.428912 AU - Manabu Shiraishi AU - Atsushi Yamaguchi AU - Ken Suzuki Y1 - 2021/01/01 UR - http://biorxiv.org/content/early/2021/03/27/2021.01.29.428912.abstract N2 - Appropriate fibrotic tissue formation after myocardial infarction (MI) is crucial to maintain the heart structure. Reparative or M2-like macrophages play a vital role in fibrosis by activating cardiac fibroblasts after MI. This study investigated the molecular and cellular mechanisms through which post-MI fibrosis is formed by focusing on the role of the M2-like macrophage subset and examined how to control fibrosis formation. We found that cardiac fibroblasts in the infarcted mouse heart showed apoptosis and senescence, both of which are associated with the fibrotic process. Moreover, some of the molecular mechanism underlying fibrotic tissue formation in the infarcted myocardium was attenuation of apoptosis and senescence of fibroblasts by M2-like macrophage-derived neuregulin 1 (Nrg1)/epidermal growth factor receptor (ErbB) signaling. In vitro and in vivo experiments showed that selective Nrg1 receptor inhibition exacerbated senescence of cardiac fibroblasts, which resulted in excessive progression of fibrosis. These results highlight previously unidentified anti-apoptotic and anti-senescence effects of the Nrg1/ErbB signaling system on cardiac fibroblasts after MI.Competing Interest StatementThe authors have declared no competing interest. ER -