β2-微球蛋白调节周围神经损伤时细胞外基质动力学。

IF 2 Q3 CLINICAL NEUROLOGY
NeuroSci Pub Date : 2025-06-29 DOI:10.3390/neurosci6030059
Eiki Shirasawa, Kentaro Uchida, Kenji Onuma, Gen Inoue, Koji Eshima, Masashi Satoh, Masayuki Miyagi, Yoji Toyomura, Akira Norisugi, Masashi Takaso
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引用次数: 0

摘要

周围神经损伤引发了一系列复杂的级联反应,包括免疫反应、细胞外基质(ECM)重塑和神经元修复。虽然β2-微球蛋白(B2M)因其在MHC i类介导的抗原呈递和CD8+ t细胞分化中的作用而闻名,但其对非免疫过程的潜在贡献仍未得到充分探讨。在这项研究中,我们利用野生型和B2M缺陷型(B2M- ko)小鼠的慢性收缩损伤(CCI)模型研究了B2M在周围神经再生中的作用。采用流式细胞术、RNA测序(RNA-seq)和定量PCR (qPCR)评估损伤后t细胞亚群动态和基因表达。流式细胞术分析显示,损伤后第7天CD3+CD4+和CD3+CD8+ t细胞群增加。两组小鼠均出现CD3+CD4+ T细胞扩增,但仅在野生型小鼠中观察到CD3+CD8+ T细胞显著增加。损伤后3天的RNA-seq分析显示,在大量t细胞积累之前,B2M-KO小鼠的ECM相关基因显著下调,包括胶原、基质相关蛋白和其他关键的ECM成分。KEGG分析发现ecm受体相互作用、PI3K-Akt和TGF-β信号通路受到抑制。qPCR证实B2M-KO小鼠中Thbs1表达降低。这些发现表明,在早期神经修复过程中,B2M在调节ECM动力学和再生信号方面发挥着关键的、不依赖CD8+ t细胞的作用,扩展了B2M功能的概念框架,超出了经典的免疫作用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

β2-Microglobulin Regulates Extracellular Matrix Dynamics During Peripheral Nerve Injury.

β2-Microglobulin Regulates Extracellular Matrix Dynamics During Peripheral Nerve Injury.

β2-Microglobulin Regulates Extracellular Matrix Dynamics During Peripheral Nerve Injury.

β2-Microglobulin Regulates Extracellular Matrix Dynamics During Peripheral Nerve Injury.

Peripheral nerve injury initiates a complex cascade of events coordinating immune responses, extracellular matrix (ECM) remodeling, and neuronal repair. While β2-microglobulin (B2M) is well known for its role in MHC class I-mediated antigen presentation and CD8+ T-cell differentiation, its potential contributions to non-immune processes remain underexplored. In this study, we investigated the role of B2M in peripheral nerve regeneration using a chronic constriction injury (CCI) model in wild-type and B2M-deficient (B2M-KO) mice. Flow cytometry, RNA sequencing (RNA-seq), and quantitative PCR (qPCR) were performed to assess T-cell subset dynamics and gene expression following injury. Flow cytometric analysis showed that CD3+CD4+ and CD3+CD8+ T-cell populations increased by day 7 post-injury. While CD3+CD4+ T-cell expansion occurred in both groups, a significant increase in CD3+CD8+ T cells was observed only in wild-type mice. RNA-seq analysis at 3 days post-injury-prior to substantial T-cell accumulation-revealed marked downregulation of ECM-related genes in B2M-KO mice, including collagens, matrix-associated proteins, and other key ECM components. KEGG analysis identified suppression of ECM-receptor interaction, PI3K-Akt, and TGF-β signaling pathways. qPCR confirmed reduced expression of Thbs1 in B2M-KO mice. These findings suggest that B2M plays a critical, CD8+ T-cell-independent role in regulating ECM dynamics and regenerative signaling during early nerve repair, expanding the conceptual framework of B2M's function beyond classical immune roles.

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