title: The Repair of Skeletal Muscle Requires Iron Recycling through Macrophage Ferroportin.
abstract: Macrophages recruited at the site of sterile muscle damage play an essential role in the regeneration of the tissue. In this article, we report that the selective disruption of macrophage ferroportin (Fpn) results in iron accumulation within muscle-infiltrating macrophages and jeopardizes muscle healing, prompting fat accumulation. Macrophages isolated from the tissue at early time points after injury express ferritin H, CD163, and hemeoxygenase-1, indicating that they can uptake heme and store iron. At later time points they upregulate Fpn expression, thus acquiring the ability to release the metal. Transferrin-mediated iron uptake by regenerating myofibers occurs independently of systemic iron homeostasis. The inhibition of macrophage iron export via the silencing of Fpn results in regenerating muscles with smaller myofibers and fat accumulation. These results highlight the existence of a local pathway of iron recycling that plays a nonredundant role in the myogenic differentiation of muscle precursors, limiting the adipose degeneration of the tissue.
authors.affiliation: Division of Immunology, Transplantation and Infectious Diseases, San Raffaele Scientific Institute, 20132 Milan, Italy; corna.gianfranca@hsr.it rovere.patrizia@hsr.it.
authors.forename: Gianfranca
authors.initials: G
authors.lastname: Corna
authors.affiliation: Division of Immunology, Transplantation and Infectious Diseases, San Raffaele Scientific Institute, 20132 Milan, Italy; Vita-Salute San Raffaele University, 20132 Milan, Italy;
authors.forename: Imma
authors.initials: I
authors.lastname: Caserta
authors.affiliation: Division of Immunology, Transplantation and Infectious Diseases, San Raffaele Scientific Institute, 20132 Milan, Italy;
authors.forename: Antonella
authors.initials: A
authors.lastname: Monno
authors.affiliation: Department of Experimental and Applied Medicine, Section of Occupational Health and Industrial Hygiene, University of Brescia, 25123 Brescia, Italy; and.
authors.forename: Pietro
authors.initials: P
authors.lastname: Apostoli
authors.affiliation: Division of Immunology, Transplantation and Infectious Diseases, San Raffaele Scientific Institute, 20132 Milan, Italy; Vita-Salute San Raffaele University, 20132 Milan, Italy;
authors.forename: Angelo A
authors.initials: AA
authors.lastname: Manfredi
authors.affiliation: Vita-Salute San Raffaele University, 20132 Milan, Italy; Division of Genetics and Cell Biology, San Raffaele Scientific Institute, 20132 Milan, Italy.
authors.forename: Clara
authors.identifier: 0000-0003-1427-0143
authors.initials: C
authors.lastname: Camaschella
authors.affiliation: Division of Immunology, Transplantation and Infectious Diseases, San Raffaele Scientific Institute, 20132 Milan, Italy; Vita-Salute San Raffaele University, 20132 Milan, Italy; corna.gianfranca@hsr.it rovere.patrizia@hsr.it.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Rovere-Querini
mesh_terms: D000273:Adipose Tissue / Q000502:physiology / Q000503:physiopathology; D000818:Animals; D015703:Antigens, CD / Q000235:genetics; D015214:Antigens, Differentiation, Myelomonocytic / Q000235:genetics; D027682:Cation Transport Proteins / Q000172:deficiency / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D006418:Heme / Q000378:metabolism; D051547:Heme Oxygenase-1 / Q000235:genetics; D006706:Homeostasis; D007501:Iron / Q000378:metabolism*; D008264:Macrophages / Q000737:chemistry* / Q000276:immunology / Q000473:pathology; D051379:Mice; D018482:Muscle, Skeletal / Q000166:cytology / Q000276:immunology / Q000502:physiology*; D009210:Myofibrils / Q000473:pathology / Q000502:physiology; D011956:Receptors, Cell Surface / Q000235:genetics; D012038:Regeneration; D014168:Transferrin / Q000378:metabolism; D014945:Wound Healing; D000098902:CD163 Antigen; D000098742:Ferroportin
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D000098902:CD163 Antigen; D027682:Cation Transport Proteins; D011956:Receptors, Cell Surface; D014168:Transferrin; D000098742:Ferroportin; D006418:Heme; D007501:Iron; D051547:Heme Oxygenase-1