Supplementary immunocytochemistry of hepatocyte growth factor production in activated macrophages early in muscle regeneration.
Supplementary immunocytochemistry of hepatocyte growth factor production in activated macrophages early in muscle regeneration.
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DOI：
10.1111/asj.12264
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发表时间：
2014-12
期刊：
影响因子：
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通讯作者：
S. Sawano;Takahiro Suzuki;Mai-Khoi Q. Do;H. Ohtsubo;W. Mizunoya;Y. Ikeuchi;R. Tatsumi
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文献类型：
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作者：
S. Sawano;Takahiro Suzuki;Mai-Khoi Q. Do;H. Ohtsubo;W. Mizunoya;Y. Ikeuchi;R. Tatsumi
再生的肌内运动神经支配被认为存在于轴突引导分子的时空表达中。我们以前的研究表明，在肌肉损伤的早期分化阶段，驻留的肌源性干细胞，即卫星细胞，会上调一种分泌的神经化学物质信号素3A(Sema3A)，以响应受损肌肉中肝细胞生长因子(HGF)的升高。然而，HGF释放的旁分泌来源仍然未知。最近，我们提出了一种可能的抗炎作用的巨噬细胞(CD206阳性的M2)，表明M2细胞主要在早期分化阶段(损伤后3-5天)渗透，并产生/分泌大量HGF。然而，在理解这一概念时，仍然有必要研究吞噬致炎巨噬细胞(CD86阳性的M1)是否在肌肉损伤时产生HGF，这是另一种仍存在于相关早期分化阶段的激活表型。目前的免疫细胞化学研究表明，心脏毒素损伤的胫前肌在第5天制备的M1表达HGF为阴性，而作为阳性对照的M2表达强烈的荧光信号。这一补充结果促进了我们对M2群体(而不是M1群体)HGF分泌的时空爆发的理解，以影响Sema3A的表达，这确保了在肌肉再生的早期阶段，运动神经元终末附着到受损和生成纤维上的协调延迟。
Regenerative intramuscular motor-innervation is thought to reside in the spatiotemporal expression of axon-guidance molecules. Our previous studies showed that resident myogenic stem cells, satellite cells, up-regulate a secreted neural-chemorepellent semaphorin 3A (Sema3A) during the early-differentiation period, in response to hepatocyte growth factor (HGF) elevated in injured muscle. However, a paracrine source of the HGF release is still unknown. Very recently, we proposed a possible contribution of anti-inflammatory macrophages (CD206-positive M2) by showing that M2 cells infiltrate predominantly at the early-differentiation phase (3-5 days post-injury) and produce/secrete large amounts of HGF. However, in understanding this concept there still remains a critical need to examine if phagocytotic pro-inflammatory macrophages (CD86-positive M1), another activated-phenotype still present at the early-differentiation phase concerned, produce HGF upon muscle injury. The current immunocytochemical study demonstrated that the HGF expression is negative for M1 prepared from cardiotoxin-injured Tibialis anterior muscle at day 5, in contrast to the intense fluorescent-signal of M2 served as a positive control. This supplementary result advances our understanding of a spatiotemporal burst of HGF secretion from M2 populations (not M1) to impact Sema3A expression, which ensures a coordinated delay in attachment of motoneuron terminals onto damaged and generating fibers during the early phase of muscle regeneration.