Macrophages (MPs) are immune cells which are crucial for tissue repair. In skeletal muscle regeneration, pro-inflammatory cells first infiltrate to promote myogenic cell proliferation, then they switch into an anti-inflammatory phenotype to sustain myogenic cells differentiation and myofiber formation. This phenotypical switch is induced by dead cell phagocytosis. We previously demonstrated that the transcription factor Nfix, a member of the nuclear factor I (Nfi) family, plays a pivotal role during muscle development, regeneration and in the progression of muscular dystrophies. Here, we show that Nfix is mainly expressed by anti-inflammatory macrophages. Upon acute injury, mice deleted for Nfix in myeloid line displayed a significant defect in the process of muscle regeneration. Indeed, Nfix is involved in the macrophage phenotypical switch and macrophages lacking Nfix failed to adopt an anti-inflammatory phenotype and interact with myogenic cells. Moreover, we demonstrated that phagocytosis induced by the inhibition of the RhoA-ROCK1 pathway leads to Nfix expression and, consequently, to acquisition of the anti-inflammatory phenotype. Our study identified Nfix as a link between RhoA-ROCK1-dependent phagocytosis and the MP phenotypical switch, thus establishing a new role for Nfix in macrophage biology for the resolution of inflammation and tissue repair.
The Transcription Factor Nfix Requires RhoA-ROCK1 Dependent Phagocytosis to Mediate Macrophage Skewing during Skeletal Muscle Regeneration / M. Saclier, M. Lapi, C. Bonfanti, G. Rossi, S. Antonini, G. Messina. - In: CELLS. - ISSN 2073-4409. - 9:3(2020), pp. 708.1-708.13.
Titolo: | The Transcription Factor Nfix Requires RhoA-ROCK1 Dependent Phagocytosis to Mediate Macrophage Skewing during Skeletal Muscle Regeneration |
Autori: | MESSINA, GRAZIELLA (Corresponding) |
Parole Chiave: | Nfix; RhoA-ROCK1; macrophages; phagocytosis; skeletal muscle |
Settore Scientifico Disciplinare: | Settore BIO/17 - Istologia |
Data di pubblicazione: | 2020 |
Rivista: | |
Tipologia: | Article (author) |
Digital Object Identifier (DOI): | http://dx.doi.org/10.3390/cells9030708 |
Appare nelle tipologie: | 01 - Articolo su periodico |
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