Hspb1 and Lgals3 in spinal neurons are closely associated with autophagy following excitotoxicity based on machine learning algorithms

Excitotoxicity represents the primary cause of neuronal death following spinal cord injury (SCI). While autophagy plays a critical and intricate role in SCI, the specific mechanism underlying the relationship between excitotoxicity and autophagy in SCI has been largely overlooked. In this study, we...

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Veröffentlicht in:PloS one Jg. 19; H. 5; S. e0303235
Hauptverfasser: Yan, Lei, Li, Zihao, Li, Chuanbo, Chen, Jingyu, Zhou, Xun, Cui, Jiaming, Liu, Peng, Shen, Chong, Chen, Chu, Hong, Hongxiang, Xu, Guanhua, Cui, Zhiming
Format: Journal Article
Sprache:Englisch
Veröffentlicht: United States Public Library of Science 10.05.2024
Public Library of Science (PLoS)
Schlagworte:
Algorithms
Animals
Apoptosis
Autophagy
Bioinformatics
Calcium-binding protein
Cell culture
Cell death
Data mining
Excitotoxicity
Galectin 3 - genetics
Galectin 3 - metabolism
Gene expression
Genes
Glutamate
Glutamic acid
Glutamic Acid - metabolism
Heat-Shock Proteins - genetics
Heat-Shock Proteins - metabolism
Injury analysis
Interdisciplinary subjects
Learning algorithms
Machine Learning
Medical diagnosis
Molecular biology
Molecular Chaperones - genetics
Molecular Chaperones - metabolism
Neonates
Nervous system
Network analysis
Neurons
Neurons - metabolism
Penicillin
Protein interaction
Protein Interaction Maps
Protein-protein interactions
Proteins
Rats
Rats, Sprague-Dawley
Research methodology
S100 protein
Spinal cord
Spinal Cord - metabolism
Spinal Cord - pathology
Spinal cord injuries
Spinal Cord Injuries - genetics
Spinal Cord Injuries - metabolism
Spinal Cord Injuries - pathology
Tissue inhibitor of metalloproteinase 1
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ISSN:1932-6203, 1932-6203
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Zusammenfassung:Excitotoxicity represents the primary cause of neuronal death following spinal cord injury (SCI). While autophagy plays a critical and intricate role in SCI, the specific mechanism underlying the relationship between excitotoxicity and autophagy in SCI has been largely overlooked. In this study, we isolated primary spinal cord neurons from neonatal rats and induced excitotoxic neuronal injury by high concentrations of glutamic acid, mimicking an excitotoxic injury model. Subsequently, we performed transcriptome sequencing. Leveraging machine learning algorithms, including weighted correlation network analysis (WGCNA), random forest analysis (RF), and least absolute shrinkage and selection operator analysis (LASSO), we conducted a comprehensive investigation into key genes associated with spinal cord neuron injury. We also utilized protein-protein interaction network (PPI) analysis to identify pivotal proteins regulating key gene expression and analyzed key genes from public datasets (GSE2599, GSE20907, GSE45006, and GSE174549). Our findings revealed that six genes—Anxa2, S100a10, Ccng1, Timp1, Hspb1, and Lgals3—were significantly upregulated not only in vitro in neurons subjected to excitotoxic injury but also in rats with subacute SCI. Furthermore, Hspb1 and Lgals3 were closely linked to neuronal autophagy induced by excitotoxicity. Our findings contribute to a better understanding of excitotoxicity and autophagy, offering potential targets and a theoretical foundation for SCI diagnosis and treatment.
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ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0303235