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.
| Original language | English |
|---|---|
| Pages (from-to) | 1914-1925 |
| Number of pages | 12 |
| Journal | Journal of Immunology |
| Volume | 197 |
| Issue number | 5 |
| DOIs | |
| Publication status | Published - Sep 1 2016 |
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ASJC Scopus subject areas
- Immunology
- Medicine(all)
Cite this
The repair of skeletal muscle requires iron recycling through macrophage ferroportin. / Corna, Gianfranca; Caserta, Imma; Monno, Antonella; Apostoli, Pietro; Manfredi, Angelo A.; Camaschella, Clara; Rovere-Querini, Patrizia.
In: Journal of Immunology, Vol. 197, No. 5, 01.09.2016, p. 1914-1925.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - The repair of skeletal muscle requires iron recycling through macrophage ferroportin
AU - Corna, Gianfranca
AU - Caserta, Imma
AU - Monno, Antonella
AU - Apostoli, Pietro
AU - Manfredi, Angelo A.
AU - Camaschella, Clara
AU - Rovere-Querini, Patrizia
PY - 2016/9/1
Y1 - 2016/9/1
N2 - 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.
AB - 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.
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U2 - 10.4049/jimmunol.1501417
DO - 10.4049/jimmunol.1501417
M3 - Article
AN - SCOPUS:84983748392
VL - 197
SP - 1914
EP - 1925
JO - Journal of Immunology
JF - Journal of Immunology
SN - 0022-1767
IS - 5
ER -