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The transcription factor Foxd3 induces spinal cord ischemia-reperfusion injury by potentiating microRNA-214-dependent inhibition of Kcnk2.
Experimental & Molecular Medicine ( IF 9.5 ) Pub Date : 2020-01-21 , DOI: 10.1038/s12276-019-0370-8 Ran Li 1 , Kunchi Zhao 1 , Qing Ruan 1 , Chunyang Meng 1 , Fei Yin 1
Experimental & Molecular Medicine ( IF 9.5 ) Pub Date : 2020-01-21 , DOI: 10.1038/s12276-019-0370-8 Ran Li 1 , Kunchi Zhao 1 , Qing Ruan 1 , Chunyang Meng 1 , Fei Yin 1
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Spinal cord injury after surgical repair of the thoracic or thoracoabdominal aorta is a devastating complication that is associated with pathological changes, including inflammation, edema, and nerve cell damage. Recently, microRNA (miRNA)-modulated control of spinal cord injury has been actively investigated. This study aims to clarify the regulatory effect of miR-214-mediated inhibition of Kcnk2 following spinal cord ischemia-reperfusion injury (SCII) and the possible underlying mechanisms. SCII was induced in rats by occluding the aortic arch followed by reperfusion. Gain-of-function and loss-of-function experiments were conducted to explore the modulatory effects of Foxd3, miR-214 and Kcnk2 on PC12 cells under hypoxia/reoxygenation (H/R) conditions. MiR-214 and Kcnk2 were poorly expressed, while Foxd3 was highly expressed in the rat spinal cord tissues and H/R-treated PC12 cells. Kcnk2 overexpression enhanced the viability and inhibited the apoptosis of the H/R-treated PC12 cells. Notably, Foxd3 activated miR-214, and miR-214 targeted Kcnk2. In addition, upregulation of Kcnk2 or knockdown of Foxd3 promoted the cell viability and reduced the apoptosis of the H/R-treated PC12 cells. Overall, our study identified a novel mechanism of Foxd3/miR-214/Kcnk2 involving SCII, suggesting that either Foxd3 or miR-214 may be a novel target for the treatment of SCII.
中文翻译：
转录因子 Foxd3 通过增强 microRNA-214 依赖性 Kcnk2 抑制来诱导脊髓缺血再灌注损伤。
胸主动脉或胸腹主动脉手术修复后的脊髓损伤是一种破坏性并发症，与炎症、水肿和神经细胞损伤等病理变化相关。最近，微小RNA（miRNA）调节脊髓损伤的控制已得到积极研究。本研究旨在阐明miR-214介导的Kcnk2抑制在脊髓缺血再灌注损伤（SCII）后的调节作用及其可能的潜在机制。通过封堵主动脉弓然后再灌注来诱导大鼠 SCII。进行功能获得和功能丧失实验，以探讨缺氧/复氧（H/R）条件下 Foxd3、miR-214 和 Kcnk2 对 PC12 细胞的调节作用。 MiR-214和Kcnk2在大鼠脊髓组织和H/R处理的PC12细胞中表达较差，而Foxd3表达较高。 Kcnk2 过表达增强了 H/R 处理的 PC12 细胞的活力并抑制了细胞凋亡。值得注意的是，Foxd3 激活 miR-214，而 miR-214 靶向 Kcnk2。此外，Kcnk2 的上调或 Foxd3 的敲低可促进细胞活力并减少 H/R 处理的 PC12 细胞的凋亡。总的来说，我们的研究发现了 Foxd3/miR-214/Kcnk2 涉及 SCII 的新机制，表明 Foxd3 或 miR-214 可能是治疗 SCII 的新靶点。
更新日期：2020-01-21
中文翻译：
转录因子 Foxd3 通过增强 microRNA-214 依赖性 Kcnk2 抑制来诱导脊髓缺血再灌注损伤。
胸主动脉或胸腹主动脉手术修复后的脊髓损伤是一种破坏性并发症，与炎症、水肿和神经细胞损伤等病理变化相关。最近，微小RNA（miRNA）调节脊髓损伤的控制已得到积极研究。本研究旨在阐明miR-214介导的Kcnk2抑制在脊髓缺血再灌注损伤（SCII）后的调节作用及其可能的潜在机制。通过封堵主动脉弓然后再灌注来诱导大鼠 SCII。进行功能获得和功能丧失实验，以探讨缺氧/复氧（H/R）条件下 Foxd3、miR-214 和 Kcnk2 对 PC12 细胞的调节作用。 MiR-214和Kcnk2在大鼠脊髓组织和H/R处理的PC12细胞中表达较差，而Foxd3表达较高。 Kcnk2 过表达增强了 H/R 处理的 PC12 细胞的活力并抑制了细胞凋亡。值得注意的是，Foxd3 激活 miR-214，而 miR-214 靶向 Kcnk2。此外，Kcnk2 的上调或 Foxd3 的敲低可促进细胞活力并减少 H/R 处理的 PC12 细胞的凋亡。总的来说，我们的研究发现了 Foxd3/miR-214/Kcnk2 涉及 SCII 的新机制，表明 Foxd3 或 miR-214 可能是治疗 SCII 的新靶点。
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