TY - JOUR
T1 - Implication of anti-inflammatory macrophages in regenerative moto-neuritogenesis
T2 - Promotion of myoblast migration and neural chemorepellent semaphorin 3A expression in injured muscle
AU - Sakaguchi, Shohei
AU - Shono, Jun Ichi
AU - Suzuki, Takahiro
AU - Sawano, Shoko
AU - Anderson, Judy E.
AU - Do, Mai Khoi Q.
AU - Ohtsubo, Hideaki
AU - Mizunoya, Wataru
AU - Sato, Yusuke
AU - Nakamura, Mako
AU - Furuse, Mitsuhiro
AU - Yamada, Koji
AU - Ikeuchi, Yoshihide
AU - Tatsumi, Ryuichi
N1 - Funding Information:
The authors are grateful to Akiko Sato and Shuichi Kitaura, Kyushu University, for technical assistance on muscle injury experiments. Authors also acknowledge the generous gift of mouse HGF cDNA from Dr. Carola Ponzetto, University of Torino, Italy and technical assistance of C. Vargas and M. Wilson. This work was supported by Grants-in-Aid for Challenging Exploratory Research 23658242 , Scientific Research (B) 22380145 and Scientific Research (A) 24248045 and by the Invitation Fellowship Program for Research in Japan (S-11197) from the Japan Society for the Promotion of Science (JSPS) (all to RT). The research was also supported by Kyushu University Foundation (to JS) and funds from the Canadian Space Agency (contribution agreement 9F007-52237-001-SR) and a Discovery Grant ( 171302 ) from the Natural Sciences and Engineering Research Council (to JEA). T. Suzuki received JSPS Pre/Post-Doctoral Research fellowships for Young Scientists and Grants-in-Aid for JSPS Fellows. S. Sawano received JSPS Research fellowships for Young Scientists and Grants-in-Aid for JSPS Fellows. M.-K. Q. Do received a scholarship from the Ministry of Education, Culture, Sports, Science and Technology —Japan (MEXT).
Publisher Copyright:
©2014 Elsevier Ltd. All rights reserved.
PY - 2014/9
Y1 - 2014/9
N2 - 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.
AB - 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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U2 - 10.1016/j.biocel.2014.05.032
DO - 10.1016/j.biocel.2014.05.032
M3 - Article
C2 - 24886696
AN - SCOPUS:84925332207
VL - 54
SP - 272
EP - 285
JO - International Journal of Biochemistry
JF - International Journal of Biochemistry
SN - 1357-2725
ER -