Piezo1 deletion ameliorates inflammation and functional recovery in spinal cord injury through altering microglia/macrophage phenotype

IF 2.7 4区医学 Q3 NEUROSCIENCES

Brain Research Pub Date : 2025-07-01 DOI:10.1016/j.brainres.2025.149810

Weiwei Zheng , Zeyu Han , Zonghan Xu , Lang Bai , Yu Zhang , Yixin Shen

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Abstract

Disruption of their homeostasis post-spinal cord injury (SCI) triggers severe secondary inflammation. This study focuses on Piezo1, a key mediator of macrophage/microglia-driven neuroinflammation. We aimed to promulgate the effect of deleting or inhibiting macrophage/microglial Piezo1 on the neural function after SCI in vitro and vivo. Here, we used C57BL/6J mice in which Piezo1 was specifically deleted in macrophages/microglia (Piezo1-CKO, Piezo1 [flox/flox, Cx3cr1-Cre]). We investigated the expression dynamics of Piezo1 following SCI, explored the phenotypic switching of macrophages/microglia under inflammatory cytokine stimulation, and examined the changes in hindlimb motor function in Piezo1-deficient mice. Our data demonstrated that macrophages/microglia in the injured segment gathered and activated after SCI, and the number of Pierzo1 + macrophages/microglia reached the peak at the 7th day. Piezo1 leads to pro-inflammatory response of macrophages/microglia with IFNγ/LPS stimulation, while inhibition of Piezo1 can lead to anti-inflammation under IL4/IL13 stimulation. Subsequently, Piezo1-CKO mice exhibited a faster and better recovery of neural function after SCI. These findings suggested that Piezo1 deletion ameliorates inflammation and functional recovery in spinal cord injury through altering microglia/macrophage phenotype.

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Piezo1缺失通过改变小胶质细胞/巨噬细胞表型改善脊髓损伤的炎症和功能恢复

脊髓损伤（SCI）后体内平衡的破坏会引发严重的继发性炎症。这项研究的重点是Piezo1，巨噬细胞/小胶质细胞驱动的神经炎症的关键介质。我们旨在揭示巨噬细胞/小胶质细胞Piezo1在体外和体内对脊髓损伤后神经功能的影响。在这里，我们使用巨噬细胞/小胶质细胞特异性缺失Piezo1的C57BL/6J小鼠（Piezo1- cko, Piezo1 [flox/flox, Cx3cr1-Cre]）。我们研究了脊髓损伤后Piezo1的表达动态，探讨了炎症细胞因子刺激下巨噬细胞/小胶质细胞的表型转换，并检测了Piezo1缺陷小鼠后肢运动功能的变化。我们的数据显示，脊髓损伤后，损伤节段的巨噬细胞/小胶质细胞聚集并激活，Pierzo1 +巨噬细胞/小胶质细胞数量在第7天达到峰值。在IFNγ/LPS刺激下，Piezo1可导致巨噬细胞/小胶质细胞的促炎反应，而在IL4/IL13刺激下，抑制Piezo1可导致抗炎反应。随后，Piezo1-CKO小鼠在脊髓损伤后表现出更快更好的神经功能恢复。这些发现表明，Piezo1缺失通过改变小胶质细胞/巨噬细胞表型来改善脊髓损伤的炎症和功能恢复。

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

Brain Research 医学-神经科学

CiteScore

5.90

自引率

3.40%

发文量

268

审稿时长

47 days

期刊介绍： An international multidisciplinary journal devoted to fundamental research in the brain sciences. Brain Research publishes papers reporting interdisciplinary investigations of nervous system structure and function that are of general interest to the international community of neuroscientists. As is evident from the journals name, its scope is broad, ranging from cellular and molecular studies through systems neuroscience, cognition and disease. Invited reviews are also published; suggestions for and inquiries about potential reviews are welcomed. With the appearance of the final issue of the 2011 subscription, Vol. 67/1-2 (24 June 2011), Brain Research Reviews has ceased publication as a distinct journal separate from Brain Research. Review articles accepted for Brain Research are now published in that journal.