Academic Journal
Inhibition of UTX/KDM6A improves recovery of spinal cord injury by attenuating BSCB permeability and macrophage infiltration through the MLCK/p-MLC pathway
| العنوان: | Inhibition of UTX/KDM6A improves recovery of spinal cord injury by attenuating BSCB permeability and macrophage infiltration through the MLCK/p-MLC pathway |
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| المؤلفون: | Xie, Yong, Luo, Zixiang, Peng, Wei, Liu, Yudong, Yuan, Feifei, Xu, Jiaqi, Sun, Yi, Lu, Hongbin, Wu, Tianding, Jiang, Liyuan, Hu, Jianzhong |
| المساهمون: | National Natural Science Foundation of China, Science and Technology Major Project of Changsha |
| المصدر: | Journal of Neuroinflammation ; volume 20, issue 1 ; ISSN 1742-2094 |
| بيانات النشر: | Springer Science and Business Media LLC |
| سنة النشر: | 2023 |
| الوصف: | Spinal cord injury (SCI) can prompt an immediate disruption to the blood–spinal cord barrier (BSCB). Restoring the integrity of this barrier is vital for the recovery of neurological function post-SCI. The UTX protein, a histone demethylase, has been shown in previous research to promote vascular regeneration and neurological recovery in mice with SCI. However, it is unclear whether UTX knockout could facilitate the recovery of the BSCB by reducing its permeability. In this study, we systematically studied BSCB disruption and permeability at different time points after SCI and found that conditional UTX deletion in endothelial cells (ECs) can reduce BSCB permeability, decrease inflammatory cell infiltration and ROS production, and improve neurological function recovery after SCI. Subsequently, we used RNA sequencing and ChIP-qPCR to confirm that conditional UTX knockout in ECs can down-regulate expression of myosin light chain kinase (MLCK), which specifically mediates myosin light chain (MLC) phosphorylation and is involved in actin contraction, cell retraction, and tight junctions (TJs) protein integrity. Moreover, we found that MLCK overexpression can increase the ratio of p-MLC/MLC, further break TJs, and exacerbate BSCB deterioration. Overall, our findings indicate that UTX knockout could inhibit the MLCK/p-MLC pathway, resulting in decreased BSCB permeability, and ultimately promoting neurological recovery in mice. These results suggest that UTX is a promising new target for treating SCI. Graphical Abstract |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.1186/s12974-023-02936-1 |
| DOI: | 10.1186/s12974-023-02936-1.pdf |
| DOI: | 10.1186/s12974-023-02936-1/fulltext.html |
| الاتاحة: | http://dx.doi.org/10.1186/s12974-023-02936-1 https://link.springer.com/content/pdf/10.1186/s12974-023-02936-1.pdf https://link.springer.com/article/10.1186/s12974-023-02936-1/fulltext.html |
| Rights: | https://creativecommons.org/licenses/by/4.0 ; https://creativecommons.org/licenses/by/4.0 |
| رقم الانضمام: | edsbas.FEFA4199 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1186/s12974-023-02936-1 |
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