Phagocytosis mediated by scavenger receptor class BI promotes macrophage transition during skeletal muscle regeneration

• Authors: Jing Zhang, Capital Medical University; Chao Qu, Emory University; Taotao Li, Capital Medical University; Wei Cui, Capital Medical University; Xiaonan Wang, Emory University; Jie Du, Capital Medical University
• Journal Title: JOURNAL OF BIOLOGICAL CHEMISTRY
• Volume: Volume 294, Number 43
• Publisher: AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC | 2019-10-25, Pages 15672-15685
• Type of Work: Article | Final Publisher PDF
• Publisher DOI: http://doi.org/10.1074/jbc.RA119.008795
• Subjects: Biology, Cell; Chemistry, Biochemistry; Biology, Molecular
• Keywords: Science & Technology; Life Sciences & Biomedicine; Biochemistry & Molecular Biology; muscle regeneration; scavenger receptor; macrophage; phagocytosis; inflammation; macrophage transition; scavenger receptor class BI; GROWTH-FACTOR-BETA; APOPTOTIC CELLS; SR-BI; DIFFERENTIATION; PROLIFERATION; INFLAMMATION; METABOLISM; ACTIVATION; EXPRESSION; PATHOLOGY

Abstract

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 anM1phenotype 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.