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Runx2 抑制小鼠脊髓损伤后的星形胶质细胞激活和星形胶质瘢痕形成。

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

机构信息

Department of Emergency, The Second Affiliated Hospital and Yuying Children's Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, 325027, China.

Department of Ultrasound, Dongtou District People's Hospital, Wenzhou, Zhejiang, 325700, China.

出版信息

Mol Neurobiol. 2024 Dec;61(12):10820-10829. doi: 10.1007/s12035-024-04212-6. Epub 2024 May 25.

DOI:10.1007/s12035-024-04212-6
PMID:38789894
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11584425/
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.

摘要

脊髓损伤后,星形胶质细胞发生反应性过程并形成星形胶质瘢痕,这阻碍了轴突的再生。Runx2 在促进中枢神经系统星形胶质细胞转化中的作用已得到充分证实。然而,目前尚不清楚 Runx2 是否也在星形胶质瘢痕的形成中发挥作用,其确切的潜在机制尚未确定。最近,我们使用细胞培养和动物模型的研究表明,Runx2 实际上抑制了损伤后星形胶质细胞的激活和星形胶质瘢痕的形成。初步结果表明,体内损伤后星形胶质细胞中 Runx2 的表达增加。随后,Runx2 的过表达导致星形胶质细胞激活的抑制、星形胶质瘢痕总面积的减少以及损伤后 14 天神经功能的恢复。然而,CADD522 逆转了这些效应。这些发现表明 Runx2 可能成为脊髓损伤 (SCI) 的一种治疗干预手段。此外,我们的研究结果表明,Runx2 的核基质靶向信号(NMTS)与其作用相关。总之,该研究的结果表明,靶向 Runx2 可能是治疗 SCI 中反应性星形胶质细胞和星形胶质瘢痕的有前途的方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e65d/11584425/355287aa92f7/12035_2024_4212_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e65d/11584425/9d692c98738d/12035_2024_4212_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e65d/11584425/7fc6be1216de/12035_2024_4212_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e65d/11584425/425da6af0ca4/12035_2024_4212_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e65d/11584425/1feee97dbb25/12035_2024_4212_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e65d/11584425/9e1e38156a69/12035_2024_4212_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e65d/11584425/355287aa92f7/12035_2024_4212_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e65d/11584425/9d692c98738d/12035_2024_4212_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e65d/11584425/7fc6be1216de/12035_2024_4212_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e65d/11584425/425da6af0ca4/12035_2024_4212_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e65d/11584425/1feee97dbb25/12035_2024_4212_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e65d/11584425/9e1e38156a69/12035_2024_4212_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e65d/11584425/355287aa92f7/12035_2024_4212_Fig6_HTML.jpg

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