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Brachial Plexus Root Avulsion Injury-Induced Endothelin-Converting Enzyme-Like 1 Overexpression Is Associated with Injured Motor Neurons Survival

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Abstract

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.

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Data Availability

All data generated or analyzed during this study are included in this published article.

Abbreviations

ANOVA:

Variance analysis

ATF-3:

Activating transcriptional factor 3

BPRA:

Brachial plexus root avulsion

CNS:

Central nervous system

DINE:

Damage-induced neuronal endopeptidase

dpi:

Days post-injury

ECEL1:

Endothelin-converting enzyme-like 1

LIF:

Leukemia inhibitory factor

MNs:

Motor neurons

NGF:

Nerve growth factor

PNS:

Peripheral nervous system

RGCs:

Retinal ganglion cells

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Acknowledgements

To the National Natural Science Foundation of China, the Natural Science Foundation of Guangdong Province of China, Open Project of Guangdong Provincial Key Laboratory of Traditional Chinese Medicine Emergency Research, and Guang Dong Basic and Applied Basic Research Foundation for providing financial support.

Funding

This work was supported by the National Natural Science Foundation of China, No. 82171369; the National Natural Science Foundation of China, No. 82102107, the Natural Science Foundation of Guangdong Province of China, No. 2021A1515012165; 2020 Open Project of Guangdong Provincial Key Laboratory of Traditional Chinese Medicine Emergency Research, No. JZ2020KF02; and the Guang Dong Basic and Applied Basic Research Foundation, No. 2022A1515110189.

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Authors and Affiliations

  1. Department of Pharmacy, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, 107 Yanjiang West Road, Guangzhou, 510120, Guangdong, China

    Ke Zhong

  2. Department of Anatomy, School of Medicine (Shenzhen), Sun Yat-sen University, Shenzhen, Guangdong, China

    Yu Huang, Yunlin Mai, Shiqin Lv, Pingzhen Wu & Lihua Zhou

  3. Center of Cyclotron and PET Radiopharmaceuticals, Department of Nuclear Medicine and PET/CT-MRI Center, The First Affiliated Hospital of Jinan University, Guangzhou, Guangdong, China

    Weijian Ye

  4. Department of Anatomy, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong, China

    Yingying Zhou

  5. Department of Radiology, The Fifth Affiliated Hospital, Sun Yat-sen University, 52 Mei Hua East Road, Zhuhai, 519000, Guangdong, China

    Yingqin Li

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  1. Yu Huang
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Contributions

Conceptualization: YL, KZ; methodology: YH, YM, SL, YZ, PW, LZ; formal analysis: YH; investigation: YH and KZ; writing—original draft preparation: YH and KZ; writing—review and editing: YH and WY; supervision: YL and KZ; project administration: YL, KZ. All authors read and approved the final manuscript.

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Correspondence to Yingqin Li or Ke Zhong.

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Huang, Y., Mai, Y., Ye, W. et al. Brachial Plexus Root Avulsion Injury-Induced Endothelin-Converting Enzyme-Like 1 Overexpression Is Associated with Injured Motor Neurons Survival. Mol Neurobiol (2024). https://doi.org/10.1007/s12035-023-03887-7

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