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.
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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.
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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) |