Brachial Plexus Root Avulsion Injury-Induced Endothelin-Converting Enzyme-Like 1 Overexpression Is Associated with Injured Motor Neurons Survival
Brachial Plexus Root Avulsion Injury-Induced Endothelin-Converting Enzyme-Like 1 Overexpression Is Associated with Injured Motor Neurons Survival
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DOI：
10.1007/s12035-023-03887-7
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发表时间：
2024-01-03
影响因子：
5.1
通讯作者：
Zhong，Ke
中科院分区：
文献类型：
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作者：
Huang，Yu;Mai，Yunlin;Zhong，Ke
臂丛神经根撕脱伤（Brachial plexus root avulsion， BPRA）是一种由分娩过程中分娩困难、运动相关事件或车祸引起的损伤，可导致运动神经元（MNs）的广泛丧失和随后的瘫痪，包括运动和感觉障碍。手术神经再植入术不能有效恢复运动功能，损伤MNs的存活对轴突再生和靶肌肉的再神经支配至关重要。因此，寻找新的分子靶点来提高损伤MNs的存活率对BPRA损伤的治疗具有重要意义。内皮素转换酶样1 （ECEL1）是一种膜结合的金属肽酶，最初被确定为与神经损伤相关的分子。不同类型的神经损伤，如视神经损伤和坐骨神经损伤后，受损神经元的ECEL1表达显著增加。本研究旨在探讨ECEL1过表达与BPRA损伤后MNs存活的关系。我们的研究结果发现，受损MNs中ECEL1的表达显著升高，并与BPRA损伤后MNs的存活呈正相关。在BPRA损伤的情况下，ECEL1的转录受转录因子c-Jun和ATF3的调控，这与以往其他神经损伤的研究结果一致。此外，在ECEL1阳性的MNs中，TrkA的表达逐渐降低，ECEL1可能保留了损伤MNs中TrkA下游AKT-GSK3β通路的活性。总之，我们的研究结果介绍了一个有希望的治疗性分子靶点，以协助再植入手术治疗BPRA损伤。
Brachial plexus root avulsion (BPRA) injury arises from challenging delivery during childbirth, sports-related incidents, or car accidents, leading to extensive loss of motor neurons (MNs) and subsequent paralysis, including both motor and sensory impairment. Surgical nerve re-implantation cannot effectively restore motor function, and the survival of injured MNs is vital for axon regeneration and re-innervating the target muscles. Therefore, identifying novel molecular targets to improve injured MNs survival is of great significance in the treatment of BPRA injuries. Endothelin-converting enzyme-like 1 (ECEL1), a membrane-bound metallopeptidase, was initially identified as a molecule associated with nerve injuries. Damaged neurons exhibit a significant increase in the expression of ECEL1 following various types of nerve injuries, such as optic nerve injury and sciatic nerve injury. This study aimed to investigate the relationship between ECEL1 overexpression and the survival of injured MNs following BPRA injury. Our results observed a significant elevation in ECEL1 expression in injured MNs and positively correlated with MNs survival following BPRA injury. The transcription of ECEL1 is regulated by the transcription factors c-Jun and ATF3 in the context of BPRA injury, which is consistent with previous other nerve injuries study. In addition, the expression of TrkA gradually decreases in ECEL1-positive MNs and ECEL1 possibly preserves the activity of downstream AKT-GSK3β pathway of TrkA in injured MNs. In conclusion, our results introduce a promising therapeutic molecular target to assist re-implantation surgery for the treatment of BPRA injury.