Bioinformatics and validation reveal spinal cord cathepsin S potential degradation of perineuronal nets in neuropathic pain

IF 4.6 2区医学 Q1 NEUROSCIENCES

Neuropharmacology Pub Date : 2025-06-24 DOI:10.1016/j.neuropharm.2025.110577

Jiahui Pang , Ziwei Hu , Yubai Zhao , Xinli Liu , Bo Wang , Qian Fang , Yin Xu , Yingxuan Hu , Hui Zeng , Wen Wu

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Abstract

Neuropathic pain (NP), resulting from nerve damage or diseases, significantly impacts patients’ quality of life. Bioinformatics analysis can assist researchers in identifying key molecular pathways involved disease progression. This study aims to investigate the hub genes in the spinal cord of NP rats, with a particular focus on the relationship between Cathepsin S (CTSS) and perineuronal nets (PNNs). Bioinformatics analysis identified Ctss as a hub gene in NP dataset GSE18803. After injury, CTSS expression was significantly upregulated in the spinal cord of NP rats, and the immunofluorescence staining confirmed the degradation of PNNs in the ipsilateral spinal cord lamina V of NP rats. Furthermore, in vitro experiment demonstrated that CTSS promoted the degradation of PNNs. Finally, knockdown CTSS expression spinal cord relived pain and PNNs degradation in NP rats. These findings suggest that CTSS is upregulated in the spinal cord of NP rats and reveal CTSS potential degradation of PNNs.

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生物信息学和验证揭示脊髓组织蛋白酶S在神经性疼痛中神经元周围网的潜在降解。

神经性疼痛（Neuropathic pain， NP）是由神经损伤或疾病引起的，严重影响患者的生活质量。生物信息学分析可以帮助研究人员识别涉及疾病进展的关键分子途径。本研究旨在探讨NP大鼠脊髓中的中枢基因，特别关注组织蛋白酶S （CTSS）与神经元周围网（pnn）之间的关系。生物信息学分析发现Ctss是NP数据集GSE18803中的枢纽基因。损伤后NP大鼠脊髓CTSS表达明显上调，免疫荧光染色证实NP大鼠同侧脊髓V层中PNNs降解。此外，体外实验表明，CTSS促进了pnn的降解。最后，抑制CTSS的脊髓表达可减轻NP大鼠的疼痛和pnn的降解。这些发现表明CTSS在NP大鼠脊髓中表达上调，揭示了CTSS对pnn的潜在降解作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Neuropharmacology 医学-神经科学

CiteScore

10.00

自引率

4.30%

发文量

288

审稿时长

45 days

期刊介绍： Neuropharmacology publishes high quality, original research and review articles within the discipline of neuroscience, especially articles with a neuropharmacological component. However, papers within any area of neuroscience will be considered. The journal does not usually accept clinical research, although preclinical neuropharmacological studies in humans may be considered. The journal only considers submissions in which the chemical structures and compositions of experimental agents are readily available in the literature or disclosed by the authors in the submitted manuscript. Only in exceptional circumstances will natural products be considered, and then only if the preparation is well defined by scientific means. Neuropharmacology publishes articles of any length (original research and reviews).