Runx2 Suppresses Astrocyte Activation and Astroglial Scar Formation After Spinal Cord Injury in Mice.

IF 4.6 2区 医学 Q1 NEUROSCIENCES Molecular Neurobiology Pub Date : 2024-12-01 Epub Date: 2024-05-25 DOI:10.1007/s12035-024-04212-6
Leilei Lu, Jiazong Ye, Dafa Yi, Tengfei Qi, Tong Luo, Silei Wu, Liangliang Yang, Lei Li, Hongyu Zhang, Daqing Chen
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Abstract

After spinal cord injury, astrocytes undergo a reactive process and form an astroglial scar, which impedes the regeneration of axons. The role of Runx2 in promoting the transformation of astrocytes in the central nervous system is well-established. However, it remains unclear whether Runx2 also plays a role in the development of astroglial scar, and the precise underlying mechanism has yet to be identified. Recently, our study using cell culture and animal models has demonstrated that Runx2 actually suppresses astrocyte activation and the formation of astroglial scar following injury. The initial results demonstrated an increase in the expression of Runx2 in astrocytes following in vivo injury. Subsequently, the overexpression of Runx2 resulted in the inhibition of astrocyte activation, reduction in the total area of astroglial scar, and restoration of neural function after 14 days of injury. However, these effects were reversed by CADD522. These findings indicate that Runx2 could potentially serve as a therapeutic intervention for spinal cord injury (SCI). Furthermore, our findings suggest that the Nuclear-matrix-targeting signal (NMTS) of Runx2 is associated with its effect. In summary, the study's results propose that targeting Runx2 may be a promising treatment approach for reactive astrocytes and astroglial scar in the recovery of SCI.

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Runx2 可抑制小鼠脊髓损伤后星形胶质细胞的活化和星形胶质细胞瘢痕的形成
脊髓损伤后,星形胶质细胞会发生反应,形成星形胶质疤痕,阻碍轴突再生。Runx2 在中枢神经系统中促进星形胶质细胞转化的作用已得到证实。然而,Runx2 是否也在星形胶质细胞瘢痕的形成过程中发挥作用仍不清楚,其确切的内在机制也有待确定。最近,我们利用细胞培养和动物模型进行的研究证明,Runx2 实际上抑制了星形胶质细胞的活化和损伤后星形胶质细胞瘢痕的形成。最初的研究结果表明,体内损伤后,Runx2 在星形胶质细胞中的表达增加。随后,Runx2 的过表达抑制了星形胶质细胞的活化,减少了星形胶质细胞瘢痕的总面积,并在损伤 14 天后恢复了神经功能。然而,CADD522 会逆转这些效应。这些研究结果表明,Runx2 有可能成为脊髓损伤(SCI)的治疗干预措施。此外,我们的研究结果还表明,Runx2的核基质靶向信号(NMTS)与其作用有关。总之,研究结果表明,靶向 Runx2 可能是治疗 SCI 恢复过程中反应性星形胶质细胞和星形胶质瘢痕的一种很有前景的方法。
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来源期刊
Molecular Neurobiology
Molecular Neurobiology 医学-神经科学
CiteScore
9.00
自引率
2.00%
发文量
480
审稿时长
1 months
期刊介绍: Molecular Neurobiology is an exciting journal for neuroscientists needing to stay in close touch with progress at the forefront of molecular brain research today. It is an especially important periodical for graduate students and "postdocs," specifically designed to synthesize and critically assess research trends for all neuroscientists hoping to stay active at the cutting edge of this dramatically developing area. This journal has proven to be crucial in departmental libraries, serving as essential reading for every committed neuroscientist who is striving to keep abreast of all rapid developments in a forefront field. Most recent significant advances in experimental and clinical neuroscience have been occurring at the molecular level. Until now, there has been no journal devoted to looking closely at this fragmented literature in a critical, coherent fashion. Each submission is thoroughly analyzed by scientists and clinicians internationally renowned for their special competence in the areas treated.
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