Unveiling the Therapeutic Potential of Baicalin in Intervertebral Disc Degeneration: Integrative Bulk and Single-Cell Transcriptome Analysis with Experimental Validation of PANoptosis Inhibition.

IF 4.2 2区医学 Q2 IMMUNOLOGY

Journal of Inflammation Research Pub Date : 2025-05-30 eCollection Date: 2025-01-01 DOI:10.2147/JIR.S519179

Xiaoqiang Wang, Silong Gao, Daqian Zhou, Weiye Cai, Jiale Lv, Zhangchao Wei, Chao Song, Xubin Shan, Zongchao Liu

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引用次数: 0

Abstract

Background: Programmed cell death (PCD), including pyroptosis, apoptosis, and necroptosis, plays a critical role in the pathogenesis of intervertebral disc degeneration (IVDD). PANoptosis, a recently identified form of PCD integrating pyroptosis, apoptosis, and necroptosis, may represent a more comprehensive target for therapeutic intervention in IVDD.

Objective: To explore the role of PANoptosis in IVDD and investigate the therapeutic potential and underlying mechanism of baicalin in regulating PANoptosis to alleviate disc degeneration.

Methods: We performed integrative analyses of bulk transcriptomic datasets (GSE167199, GSE245147, GSE266883) and a single-cell RNA-seq dataset (GSE244889) to identify PANoptosis-related genes involved in IVDD. The expression and function of key genes were validated using clinical samples, an IL-1β-induced NPC degeneration model in vitro, and a puncture-induced rat IVDD model in vivo treated with baicalin.

Results: Five core PANoptosis-related genes (FOS, CASP1, H1-2, BCL2L11, and H2AC6) were significantly upregulated in degenerated discs. Baicalin treatment effectively downregulated these genes at both mRNA and protein levels. Moreover, baicalin alleviated IL-1β-induced cell death in NPCs and improved histological features in the rat IVDD model.

Conclusion: Our findings reveal a critical role of PANoptosis in IVDD progression and demonstrate that baicalin alleviates disc degeneration by inhibiting PANoptosis. This study provides novel insights into PANoptosis as a promising therapeutic target for IVDD.

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揭示黄芩苷对椎间盘退变的治疗潜力：综合体和单细胞转录组分析与PANoptosis抑制的实验验证。

背景：程序性细胞死亡（PCD），包括焦亡、凋亡和坏死下垂，在椎间盘退变（IVDD）的发病机制中起关键作用。PANoptosis是最近发现的一种PCD形式，集焦亡、凋亡和坏死坏死于一体，可能是IVDD治疗干预的更全面的靶点。目的：探讨PANoptosis在IVDD中的作用，探讨黄芩苷调节PANoptosis减轻椎间盘退变的治疗潜力及机制。方法：我们对大量转录组数据集（GSE167199, GSE245147, GSE266883）和单细胞RNA-seq数据集（GSE244889）进行综合分析，以鉴定参与IVDD的panoptosis相关基因。通过临床样品、il -1β诱导的鼻咽癌退变体外模型和黄芩苷诱导的穿刺大鼠IVDD模型验证关键基因的表达和功能。结果：5个核心panopysis相关基因（FOS、CASP1、H1-2、BCL2L11和H2AC6）在退变椎间盘中显著上调。黄芩苷处理有效下调了这些基因的mRNA和蛋白水平。黄芩苷可减轻il -1β诱导的NPCs细胞死亡，改善大鼠IVDD模型的组织学特征。结论：我们的研究结果揭示了PANoptosis在IVDD进展中的关键作用，并表明黄芩苷通过抑制PANoptosis来减轻椎间盘退变。这项研究为PANoptosis作为IVDD的有希望的治疗靶点提供了新的见解。

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

Journal of Inflammation Research Immunology and Microbiology-Immunology

CiteScore

6.10

自引率

2.20%

发文量

658

审稿时长

16 weeks

期刊介绍： An international, peer-reviewed, open access, online journal that welcomes laboratory and clinical findings on the molecular basis, cell biology and pharmacology of inflammation.