Autocrine and immune cell-derived BDNF in human skeletal muscle: implications for myogenesis and tissue regeneration
Autocrine and immune cell-derived BDNF in human skeletal muscle: implications for myogenesis and tissue regeneration
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DOI：
10.1002/path.4228
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发表时间：
2013-10-01
影响因子：
7.3
通讯作者：
Farina, Cinthia
中科院分区：
文献类型：
--
作者：
Colombo, Emanuela;Bedogni, Francesco;Farina, Cinthia
神经营养素系统在骨骼肌生物学中起作用。小鼠肌肉前体细胞中BDNF的条件性缺失改变了体内肌肉发生和再生。然而，BDNF在人类骨骼肌组织中的表达、定位和功能尚不清楚，因此啮齿类动物的发现与人类肌肉的相关性尚不清楚。在这里，我们解决这一问题，结合离体组织学研究对人类活检与体外分析的人原代肌细胞。我们发现，BDNF表达的前体细胞和分化的细胞在体外和体内。BDNF受体的差异分析显示，p75 NTR的表达，而不是在肌细胞中的TrkB，这表明BDNF-p75 NTR轴是占主导地位的人骨骼肌细胞。一些体外功能实验表明，成肌细胞培养中BDNF基因沉默或蛋白质阻断阻碍了肌生成。最后，炎性肌病活检的组织学研究显示，浸润的免疫细胞优先定位于p75 NTR阳性再生纤维附近，它们产生BDNF。总之，BDNF是骨骼肌细胞的自分泌因子，并可能调节人类肌肉发生。此外，产生BDNF的免疫细胞在p75 NTR阳性再生肌纤维附近的优先定位表明免疫细胞来源的BDNF可以维持发炎肌肉中的组织修复。版权所有（c）2013大不列颠和爱尔兰病理学会。由John Wiley & Sons有限公司出版
The neurotrophin system has a role in skeletal muscle biology. Conditional depletion of BDNF in mouse muscle precursor cells alters myogenesis and regeneration in vivo. However, the expression, localization and function of BDNF in human skeletal muscle tissue is not known, so the relevance of the rodent findings for human muscle are unknown. Here we address this by combining ex vivo histological investigations on human biopsies with in vitro analyses of human primary myocytes. We found that BDNF was expressed by precursor and differentiated cells both in vitro and in vivo. Differential analysis of BDNF receptors showed expression of p75NTR and not of TrkB in myocytes, suggesting that the BDNF-p75NTR axis is predominant in human skeletal muscle cells. Several in vitro functional experiments demonstrated that BDNF gene silencing or protein blockade in myoblast cultures hampered myogenesis. Finally, histological investigations of inflammatory myopathy biopsies revealed that infiltrating immune cells localized preferentially near p75NTR-positive regenerating fibres and that they produced BDNF. In conclusion, BDNF is an autocrine factor for skeletal muscle cells and may regulate human myogenesis. Furthermore, the preferential localization of BDNF-producing immune cells near p75NTR-positive regenerating myofibres suggests that immune cell-derived BDNF may sustain tissue repair in inflamed muscle. Copyright (c) 2013 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.