Mesenchymal stem cell transplantation ameliorates inflammation in spinal cord injury by inhibiting lactylation-related genes

IF 3.7 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Cytokine Pub Date : 2025-05-08 DOI:10.1016/j.cyto.2025.156960

Weiwei Zou , Zelin Zhang , Tingting Cao , Mangmang Li

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引用次数: 0

Abstract

Background

The immune microenvironment significantly influences neural regeneration in spinal cord injury (SCI). Lactate activates central nervous system (CNS) glial cells, prompting the secretion of proinflammatory cytokines and triggering an inflammatory response. Mesenchymal stem cells (MSCs) make a promising future for SCI therapy due to their immune regulation and anti-inflammatory properties. However, it is unclear whether MSCs inhibit inflammatory responses in the SCI microenvironment through lactylation regulation. This study aimed to identify lactylation-related genes (LRGs) in SCI and investigate their role in immune cell infiltration and MSC-mediated inflammation reduction.

Methods

Transcription datasets of SCI patients were acquired from Gene Expression Omnibus (GEO). Differentially expressed genes (DEGs) underwent functional enrichment analysis, and CIBERSORT assessed immune cell infiltration in SCI. Crucial lactylation-related differentially expressed genes (LRDEGs) associated with SCI were identified via machine learning. The association between LRDEGs and inflammatory response in SCI mediated by immune cell infiltration was confirmed using Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG). Rats with subacute thoracic SCI were transplanted with hUC-MSCs, and transcriptome analyses were conducted on their spinal cords and retrieved hUC-MSCs, respectively.

Results

The study identified 808 DEGs and 13 differentially infiltrated immune cell types in SCI patients compared to healthy controls. Multiple inflammatory response-related signaling pathways were activated in SCI. Seven LRDEGs, including LSP1, XRCC4, HSDL2, HNRNPH1, RPL14, IKZF1, and TP53, were recognized as key regulators. These genes are linked to immune cell infiltration and inflammatory responses in SCI. In SCI rats, the increased expression of LRDEGs and inflammatory cytokines were observed, which were significantly reduced after hUC-MSC transplantation. Differences in LRDEG expression patterns, enriched functions, and pathways between two SCI subtypes were statistically significant.

Conclusions

LRDEGs are involved in immune cell-mediated inflammatory response in SCI, and hUC-MSC transplantation reduces LRDEGs expression and inflammation response in the SCI microenvironment.

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间充质干细胞移植通过抑制乳酸化相关基因改善脊髓损伤的炎症

背景免疫微环境对脊髓损伤后神经再生有重要影响。乳酸激活中枢神经系统（CNS）胶质细胞，促进促炎细胞因子的分泌，引发炎症反应。间充质干细胞（MSCs）因其免疫调节和抗炎特性在脊髓损伤治疗中具有广阔的应用前景。然而，MSCs是否通过乳酸化调节抑制脊髓损伤微环境中的炎症反应尚不清楚。本研究旨在鉴定脊髓损伤中乳酸酰化相关基因（LRGs），并探讨其在免疫细胞浸润和msc介导的炎症减轻中的作用。方法从基因表达综合数据库（Gene Expression Omnibus， GEO）获取脊髓损伤患者的转录数据。差异表达基因（DEGs）进行功能富集分析，CIBERSORT评估脊髓损伤中的免疫细胞浸润。通过机器学习鉴定了与SCI相关的关键乳酸化相关差异表达基因（LRDEGs）。利用基因本体（GO）和京都基因基因组百科全书（KEGG）证实了LRDEGs与免疫细胞浸润介导的SCI炎症反应之间的关联。将亚急性胸椎脊髓损伤大鼠移植hUC-MSCs，分别对其脊髓和检索到的hUC-MSCs进行转录组分析。结果与健康对照相比，本研究在脊髓损伤患者中鉴定出808种deg和13种不同浸润的免疫细胞类型。多种炎症反应相关的信号通路在脊髓损伤中被激活。7个lrdeg，包括LSP1、XRCC4、HSDL2、HNRNPH1、RPL14、IKZF1和TP53，被认为是关键调控因子。这些基因与脊髓损伤的免疫细胞浸润和炎症反应有关。在SCI大鼠中，lrdeg和炎性细胞因子的表达增加，hUC-MSC移植后显著降低。两种SCI亚型之间LRDEG的表达模式、富集功能和通路的差异具有统计学意义。结论slrdegs参与了脊髓损伤中免疫细胞介导的炎症反应，hUC-MSC移植可降低脊髓损伤微环境中LRDEGs的表达和炎症反应。

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

Cytokine 医学-免疫学

CiteScore

7.60

自引率

2.60%

发文量

262

审稿时长

48 days

期刊介绍： The journal Cytokine has an open access mirror journal Cytokine: X, sharing the same aims and scope, editorial team, submission system and rigorous peer review. * Devoted exclusively to the study of the molecular biology, genetics, biochemistry, immunology, genome-wide association studies, pathobiology, diagnostic and clinical applications of all known interleukins, hematopoietic factors, growth factors, cytotoxins, interferons, new cytokines, and chemokines, Cytokine provides comprehensive coverage of cytokines and their mechanisms of actions, 12 times a year by publishing original high quality refereed scientific papers from prominent investigators in both the academic and industrial sectors. We will publish 3 major types of manuscripts: 1) Original manuscripts describing research results. 2) Basic and clinical reviews describing cytokine actions and regulation. 3) Short commentaries/perspectives on recently published aspects of cytokines, pathogenesis and clinical results.