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DANCR基因敲低通过调节ACTN4/STAT3轴减轻脊髓损伤后的神经炎症并促进功能恢复。

DANCR knockdown alleviates neuroinflammation and functional recovery after spinal cord injury via regulating the ACTN4 / STAT3 axis.

作者信息

Xia Bin, Yu Cheng, Liu Jin, Lin Jiezhao, Lyu Jiao, Wang Xin, Zhu Lixin

机构信息

Department of Spinal Surgery, Orthopedic Medical Center, Zhujiang Hospital, Southern Medical University, Guangzhou, 510280, China; Department of Orthopedics, Chengdu Seventh People's Hospital (Afliated Cancer Hospital of Chengdu Medical College), Chengdu, 610299, China.

Department of Spinal Surgery, Orthopedic Medical Center, Zhujiang Hospital, Southern Medical University, Guangzhou, 510280, China.

出版信息

Arch Biochem Biophys. 2025 Mar;765:110293. doi: 10.1016/j.abb.2025.110293. Epub 2025 Jan 9.

DOI:10.1016/j.abb.2025.110293
PMID:39798643
Abstract

Polarization of microglia following spinal cord injury (SCI) is a pivotal pathological process of secondary injury. Although differentiation antagonistic nonprotein coding RNA (DANCR) has been implicated in immune and inflammatory responses across various diseases, its role in SCI still unclear. This research aimed to clarify the underlying mechanisms of DANCR in SCI recovery by investigating its expression pattern in microglia. Our findings indicate that the DANCR level in microglia is increased after SCI and that its knockdown can promote microglial M2-type polarization; suppress inflammatory cytokines, oxidative stress, and neuronal apoptosis; and facilitate nerve regeneration as well as spinal cord functional recovery. Further investigations suggest that DANCR's effects are mediated through the ACTN4/STAT3 axis. These results provide potential targets for enhancing functional recovery following SCI.

摘要

脊髓损伤(SCI)后小胶质细胞的极化是继发性损伤的关键病理过程。尽管分化拮抗非蛋白质编码RNA(DANCR)已被证明参与多种疾病的免疫和炎症反应,但其在SCI中的作用仍不清楚。本研究旨在通过研究DANCR在小胶质细胞中的表达模式,阐明其在SCI恢复中的潜在机制。我们的研究结果表明,SCI后小胶质细胞中DANCR水平升高,敲低DANCR可促进小胶质细胞M2型极化;抑制炎性细胞因子、氧化应激和神经元凋亡;促进神经再生以及脊髓功能恢复。进一步研究表明,DANCR的作用是通过ACTN4/STAT3轴介导的。这些结果为增强SCI后的功能恢复提供了潜在靶点。

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