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M2\u2010like macrophages play a vital role in post\u2010MI fibrosis by activating cardiac fibroblasts. Because the mechanism by which post\u2010MI cardiac fibrosis is regulated is not fully understood, we investigated, in vitro and in vivo, the cellular and molecular mechanisms of post\u2010MI fibrotic tissue formation, especially those related to the regulation of cellular senescence and apoptosis. CD206\n                    <jats:sup>+<\/jats:sup>\n                    F4\/80\n                    <jats:sup>+<\/jats:sup>\n                    CD11b\n                    <jats:sup>+<\/jats:sup>\n                    M2\u2010like macrophages collected from mouse hearts on post\u2010MI day 7\u00a0showed increased expression of neuregulin 1 (Nrg1). Nrg1 receptor epidermal growth factor receptors ErbB2 and ErbB4 were expressed on cardiac fibroblasts in the infarct area. M2\u2010like macrophage\u2010derived Nrg1\u00a0suppressed both hydrogen peroxide\u2010induced senescence and apoptosis of fibroblasts, whereas blockade of ErbB function significantly accelerated both processes. M2\u2010like macrophage\u2010derived Nrg1\/ErbB\/PI3K\/Akt signaling, shown to be related to anti\u2010senescence, was activated in damaged cardiac fibroblasts. Interestingly, systemic blockade of ErbB function in MI model mice enhanced senescence and apoptosis of cardiac fibroblasts and exacerbated inflammation. Further, increased accumulation of M2\u2010like macrophages resulted in excessive post\u2010MI progression of fibrosis in mice hearts. The molecular mechanism underlying the regulation of fibrotic tissue formation in the infarcted myocardium was shown in part to be attenuation of apoptosis and senescence of cardiac fibroblasts by the activation of Nrg1\/ErbB\/PI3K\/Akt signaling. M2\u2010like macrophage\u2010mediated 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.\n                  <\/jats:p>","DOI":"10.1096\/fj.202101428rr","type":"journal-article","created":{"date-parts":[[2022,1,8]],"date-time":"2022-01-08T11:44:10Z","timestamp":1641642250000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":50,"title":["Nrg1\/ErbB signaling\u2010mediated regulation of fibrosis after myocardial infarction"],"prefix":"10.1096","volume":"36","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4491-7473","authenticated-orcid":false,"given":"Manabu","family":"Shiraishi","sequence":"first","affiliation":[{"name":"Department of Cardiovascular Surgery Saitama Medical Center Jichi Medical University  Saitama Japan"},{"name":"William Harvey Research 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