Overlapping Mechanisms of Peripheral Nerve Regeneration and Angiogenesis Following Sciatic Nerve Transection.

Overlapping Mechanisms of Peripheral Nerve Regeneration and Angiogenesis Following Sciatic Nerve Transection.
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坐骨神经横断后周围神经再生和血管生成的重叠机制

DOI:
10.3389/fncel.2017.00323
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发表时间:
2017
影响因子:
5.3
通讯作者:
Gu X
Gu X
中科院分区:
医学2区
文献类型:
--
作者:
Wang H;Zhu H;Guo Q;Qian T;Zhang P;Li S;Xue C;Gu X

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周围神经系统具有自我再生的能力,主要表现在其再生微环境中,包括血管网的重建。近年来,组织再生和血管生成之间的密切关系受到越来越多的关注。为探讨周围神经损伤后周围神经再生与血管生成的分子机制和关键调控分子的重叠,对SD大鼠坐骨神经切断后近端残端的微阵列数据进行了整合和生物信息学分析。坐骨神经切断后第1天,神经再生和血管生成同时被激活。转录调节因子和经典途径的更明显变化表明坐骨神经切断后1至4天神经再生和血管生成均发生了相变。此外,16个差异表达基因参与了神经再生和血管生成的重要生物学过程,其中一些通过qPCR和免疫荧光染色验证。研究表明,STAT3、EPHB3和Cdc42在雪旺细胞和血管内皮细胞中共表达,在坐骨神经切断后神经再生和血管生成的同时调控中发挥关键作用。我们提供了一个框架,了解周围神经横断后周围神经再生和血管生成之间的生物学过程和精确的分子相关性。我们的工作作为一个实验基础和一个有价值的资源,以进一步了解分子机制,定义神经损伤诱导的微环境变化,以实现所需的周围神经再生。
Peripheral nervous system owns the ability of self-regeneration, mainly in its regenerative microenvironment including vascular network reconstruction. More recently, more attentions have been given to the close relationship between tissue regeneration and angiogenesis. To explore the overlap of molecular mechanisms and key regulation molecules between peripheral nerve regeneration and angiogenesis post peripheral nerve injury, integrative and bioinformatic analysis was carried out for microarray data of proximal stumps after sciatic nerve transection in SD rats. Nerve regeneration and angiogenesis were activated at 1 day immediately after sciatic nerve transection simultaneously. The more obvious changes of transcription regulators and canonical pathways suggested a phase transition between 1 and 4 days of both nerve regeneration and angiogenesis after sciatic nerve transection. Furthermore, 16 differentially expressed genes participated in significant biological processes of both nerve regeneration and angiogenesis, a few of which were validated by qPCR and immunofluorescent staining. It was demonstrated that STAT3, EPHB3, and Cdc42 co-expressed in Schwann cells and vascular endothelial cells to play a key role in regulation of nerve regeneration and angiogenesis simultaneously response to sciatic nerve transection. We provide a framework for understanding biological processes and precise molecular correlations between peripheral nerve regeneration and angiogenesis after peripheral nerve transection. Our work serves as an experimental basis and a valuable resource to further understand molecular mechanisms that define nerve injury-induced micro-environmental variation for achieving desired peripheral nerve regeneration.
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