RRC ID 45106
著者 Sakaguchi S, Shono J, Suzuki T, Sawano S, Anderson JE, Do MK, Ohtsubo H, Mizunoya W, Sato Y, Nakamura M, Furuse M, Yamada K, Ikeuchi Y, Tatsumi R.
タイトル Implication of anti-inflammatory macrophages in regenerative moto-neuritogenesis: promotion of myoblast migration and neural chemorepellent semaphorin 3A expression in injured muscle.
ジャーナル Int J Biochem Cell Biol
Abstract Regenerative mechanisms that regulate intramuscular motor innervation are thought to reside in the spatiotemporal expression of axon-guidance molecules. Our previous studies proposed a heretofore unexplored role of resident myogenic stem cell (satellite cell)-derived myoblasts as a key presenter of a secreted neural chemorepellent semaphorin 3A (Sema3A); hepatocyte growth factor (HGF) triggered its expression exclusively at the early-differentiation phase. In order to verify this concept, the present study was designed to clarify a paracrine source of HGF release. In vitro experiments demonstrated that activated anti-inflammatory macrophages (CD206-positive M2) produce HGF and thereby promote myoblast chemoattraction and Sema3A expression. Media from pro-inflammatory macrophage cultures (M1) did not show any significant effect. M2 also enhanced the expression of myoblast-differentiation markers in culture, and infiltrated predominantly at the early-differentiation phase (3-5 days post-injury); M2 were confirmed to produce HGF as monitored by in vivo/ex vivo immunocytochemistry of CD11b/CD206/HGF-positive cells and by HGF in situ hybridization of cardiotoxin- or crush-injured tibialis anterior muscle, respectively. These studies advance our understanding of the stage-specific activation of Sema3A expression signaling. Findings, therefore, encourage the idea that M2 contribute to spatiotemporal up-regulation of extracellular Sema3A concentrations by producing HGF that, in turn, stimulates a burst of Sema3A secretion by myoblasts that are recruited to site of injury. This model may ensure a coordinated delay in re-attachment of motoneuron terminals onto damaged fibers early in muscle regeneration, and thus synchronize the recovery of muscle-fiber integrity and the early resolution of inflammation after injury.
巻・号 54
ページ 272-85
公開日 2014-9-1
DOI 10.1016/j.biocel.2014.05.032
PII S1357-2725(14)00190-3
PMID 24886696
MeSH Animals Anti-Inflammatory Agents / metabolism Blotting, Western Cell Differentiation* Cell Movement* Cells, Cultured Hepatocyte Growth Factor / metabolism In Situ Hybridization Macrophages / cytology Macrophages / drug effects Macrophages / immunology* Macrophages / metabolism Male Mice Mice, Inbred C57BL Motor Neurons / cytology* Motor Neurons / drug effects Motor Neurons / immunology Motor Neurons / metabolism Muscle, Skeletal / cytology Muscle, Skeletal / injuries Muscle, Skeletal / metabolism* Myoblasts, Skeletal / cytology Myoblasts, Skeletal / drug effects Myoblasts, Skeletal / metabolism* Nerve Regeneration / physiology* Neurogenesis / physiology RNA, Messenger / genetics Real-Time Polymerase Chain Reaction Reverse Transcriptase Polymerase Chain Reaction Semaphorin-3A / genetics Semaphorin-3A / metabolism* Signal Transduction
IF 3.673
引用数 25
WOS 分野 BIOCHEMISTRY & MOLECULAR BIOLOGY CELL BIOLOGY
リソース情報
ヒト・動物細胞 C2C12(RCB0987)