期刊
INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY
卷 54, 期 -, 页码 272-285出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.biocel.2014.05.032
关键词
Activated macrophage; Hepatocyte growth factor; Semaphorin 3A; Migration; Regenerative moto-neuritogenesis
资金
- Challenging Exploratory Research [23658242]
- Japan Society for the Promotion of Science (JSPS) [S-11197]
- Kyushu University Foundation
- Canadian Space Agency [9F007-52237-001-SR]
- Natural Sciences and Engineering Research Council [171302]
- JSPS Pre/Post-Doctoral Research fellowships
- Ministry of Education, Culture, Sports, Science and Technology-japan (MEXT)
- [22380145]
- [24248045]
- Grants-in-Aid for Scientific Research [14J40234, 23658242, 14J09964] Funding Source: KAKEN
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 immunocytochemistiy 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. (C) 2014 Elsevier Ltd. All rights reserved.
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