| First Author | Zhang J | Year | 2019 |
| Journal | J Biol Chem | Volume | 294 |
| Issue | 43 | Pages | 15672-15685 |
| PubMed ID | 31462534 | Mgi Jnum | J:283058 |
| Mgi Id | MGI:6383571 | Doi | 10.1074/jbc.RA119.008795 |
| Citation | Zhang J, et al. (2019) Phagocytosis mediated by scavenger receptor class BI promotes macrophage transition during skeletal muscle regeneration. J Biol Chem 294(43):15672-15685 |
| abstractText | Macrophages play an essential role in skeletal muscle regeneration. The phagocytosis of muscle cell debris induces a switch of pro-inflammatory macrophages into an anti-inflammatory phenotype, but the cellular receptors mediating this phagocytosis are still unclear. In this paper, we report novel roles for SRB1 (scavenger receptor class BI) in regulating macrophage phagocytosis and macrophage phenotypic transitions for skeletal muscle regeneration. In a mouse model of cardiotoxin-induced muscle injury/regeneration, infiltrated macrophages expressed a high level of SRB1. Using SRB1 knockout mice, we observed the impairment of muscle regeneration along with decreased myogenin expression and increased matrix deposit. Bone marrow transplantation experiments indicated that SRB1 deficiency in bone marrow cells was responsible for impaired muscle regeneration. Compared with WT mice, SRB1 deficiency increased pro-inflammatory macrophage number and pro-inflammatory gene expression and decreased anti-inflammatory macrophage number and anti-inflammatory gene expression in injured muscle. In vitro, SRB1 deficiency led to a strong decrease in macrophage phagocytic activity on myoblast debris. SRB1-deficient macrophages easily acquired an M1 phenotype and failed to acquire an M2 phenotype in lipopolysaccharide/myoblast debris activation. Furthermore, SRB1 deficiency promoted activation of ERK1/2 MAPK signaling in macrophages stimulated with lipopolysaccharide/myoblast debris. Taken together, SRB1 in macrophages regulates phagocytosis and promotes M1 switch into M2 macrophages, contributing to muscle regeneration. |
