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不同时间点脊髓损伤中铁死亡基因的鉴定:生物信息学和实验验证。

Identification of Ferroptotic Genes in Spinal Cord Injury at Different Time Points: Bioinformatics and Experimental Validation.

机构信息

Department of Orthopedics, The First Affiliated Hospital of Anhui Medical University, Anhui Medical University, 218 Jixi Road, Hefei, 230022, China.

School of Basic Medical Sciences, Anhui Medical University, 81 Meishan Road, Hefei, 230032, China.

出版信息

Mol Neurobiol. 2022 Sep;59(9):5766-5784. doi: 10.1007/s12035-022-02935-y. Epub 2022 Jul 7.

DOI:10.1007/s12035-022-02935-y
PMID:35796899
Abstract

Programmed cell death (PCD) is an important pathologic process after spinal cord injury (SCI). As a new type of PCD, ferroptosis is involved in the secondary SCI. However, the underlying molecular mechanism remains unclear. In this study, we validated ferroptotic phenotype in an animal model of SCI. Then, the bioinformatic analyses performed on a microarray data of SCI (GSE45006). KEGG analysis suggested that the pathways of mTOR, HIF-1, VEGF, and protein process in endoplasmic reticulum were involved in SCI-induced ferroptosis. GO analysis revealed that oxidative stress, amide metabolic process, cation transport, and cytokine production were essential biological processes in ferroptosis after SCI. We highlighted five genes including ATF-3, XBP-1, HMOX-1, DDIT-3, and CHAC-1 as ferroptotic key gene in SCI. These results contribute to exploring the ferroptotic mechanism underlying the secondary SCI and providing potential targets for clinical treatment.

摘要

程序性细胞死亡(PCD)是脊髓损伤(SCI)后的一个重要病理过程。作为一种新型的 PCD,铁死亡参与了继发性 SCI。然而,其潜在的分子机制尚不清楚。在本研究中,我们在 SCI 的动物模型中验证了铁死亡表型。然后,我们对 SCI 的微阵列数据(GSE45006)进行了生物信息学分析。KEGG 分析表明,mTOR、HIF-1、VEGF 和内质网蛋白加工途径参与了 SCI 诱导的铁死亡。GO 分析表明,氧化应激、酰胺代谢过程、阳离子转运和细胞因子产生是 SCI 后铁死亡的重要生物学过程。我们强调了五个基因,包括 ATF-3、XBP-1、HMOX-1、DDIT-3 和 CHAC-1,作为 SCI 中铁死亡的关键基因。这些结果有助于探索继发性 SCI 中铁死亡的机制,并为临床治疗提供潜在的靶点。

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