Injured sensory neurons-derived galectin-3 contributes to neuropathic pain via programming microglia in the spinal dorsal horn

Shan, Leyan; Xu, Kangtai; Ji, Luyao; Zeng, Qian; Liu, Yaqi; Wu, Yifei; Chen, Yiming; Li, Yitong; Hu, Qiaodan; Wu, Jiawei; Xu, Yuanfan; Luo, Yuhui; Li, Changlin; Wu, Chaoran; Jiang, Changyu; Wang, Zilong

doi:10.1016/j.bbi.2024.01.002

Cited by 10 publications

(1 citation statement)

References 69 publications

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“…Some studies have shown that Lgals3 can promote autophagy, while others have found that it can inhibit autophagy [82][83][84]. Recent research has revealed that Lgals3 secreted by injured neurons can activate and reprogram microglia in the spinal dorsal horn, leading to neuropathic pain [85]. Despite its association with neuroinflammation [86], Lgals3 has been overlooked in the study of neuronal autophagy.…”

Section: Plos Onementioning

confidence: 99%

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

Yan,

Li,

et al. 2024

PLoS ONE

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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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Section: Plos Onementioning

confidence: 99%

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

Yan,

Li,

et al. 2024

PLoS ONE

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Anandamide Modulates Thermal Avoidance in Caenorhabditis elegans Through Vanilloid and Cannabinoid Receptor Interplay

Abdollahi,

Castaño,

Salem

et al. 2024

Neurochem Res

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Knockdown siRNA Targeting GPR55 Reveals Significant Differences Between the Anti-inflammatory Actions of KLS-13019 and Cannabidiol

Brenneman,

Kinney,

McDonnell

et al. 2024

J Mol Neurosci

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KLS-13019 was reported previously to reverse paclitaxel-induced mechanical allodynia in a mouse model of chemotherapy-induced peripheral neuropathy (CIPN). Recent studies demonstrated that paclitaxelinduced increases in in ammatory markers (GPR55, NLRP3 and IL-1b) of dorsal root ganglion (DRG) cultures were shown to be reversed by KLS-13019 treatment. The mechanism of action for KLS-13019mediated reversal of paclitaxel-induced neuroin ammation now has been explored using GPR55 siRNA. Pretreatment of DRG cultures with GPR55 siRNA produced a 21% decrease of immunoreactive (IR) area for GPR55 in cell bodies and a 59% decrease in neuritic IR area, as determined by high content imaging. Using a 24-hour reversal treatment paradigm, paclitaxel-induced increases in the in ammatory markers were reversed back to control levels after KLS-3019 treatment. Decreases in these in ammatory markers produced by KLS-13019 were signi cantly attenuated by GPR55 siRNA co-treatment, with mean IR area responses being attenuated by 56% in neurites and 53% in cell bodies. These data indicate that the percentage decreases in siRNA-mediated attenuation of KLS-13019-related e cacy on the in ammatory markers were similar to the percentage knockdown observed for neuritic GPR55 IR area. Similar studies conducted with cannabidiol (CBD), the parent compound of KLS-13019, produced low e cacy (25%) reversal of all in ammatory markers that were poorly attenuated (29%) by GPR55 siRNA. CBD was shown previously to be ineffective in reversing paclitaxel-induced mechanical allodynia. The present studies indicated signi cant differences between the anti-in ammatory properties of KLS-13019 and CBD which may play a role in their observed differences in the reversibility of mechanical allodynia in a mouse model of CIPN.

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Injured sensory neurons-derived galectin-3 contributes to neuropathic pain via programming microglia in the spinal dorsal horn

Cited by 10 publications

References 69 publications

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

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

Anandamide Modulates Thermal Avoidance in Caenorhabditis elegans Through Vanilloid and Cannabinoid Receptor Interplay

Knockdown siRNA Targeting GPR55 Reveals Significant Differences Between the Anti-inflammatory Actions of KLS-13019 and Cannabidiol

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