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Open AccessArticle

The Transcription Factor Nfix Requires RhoA-ROCK1 Dependent Phagocytosis to Mediate Macrophage Skewing during Skeletal Muscle Regeneration

Department of Biosciences, University of Milan, via Celoria 26, 20133 Milan, Italy
Author to whom correspondence should be addressed.
Current affiliation: Laboratory of Stem Cell Bioengineering, Institute of Bioengineering, School of Life Sciences and School of Engineering, École Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, Vaud, Switzerland.
Cells 2020, 9(3), 708;
Received: 19 February 2020 / Revised: 11 March 2020 / Accepted: 12 March 2020 / Published: 13 March 2020
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. View Full-Text
Keywords: macrophages; Nfix; skeletal muscle; phagocytosis; RhoA-ROCK1 macrophages; Nfix; skeletal muscle; phagocytosis; RhoA-ROCK1
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MDPI and ACS Style

Saclier, M.; Lapi, M.; Bonfanti, C.; Rossi, G.; Antonini, S.; Messina, G. The Transcription Factor Nfix Requires RhoA-ROCK1 Dependent Phagocytosis to Mediate Macrophage Skewing during Skeletal Muscle Regeneration. Cells 2020, 9, 708.

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