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

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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.

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Acknowledgements

Schematic was generated using BioRender (www.biorender.com). We appreciate Dr. Haijian Cai (Center for Scientific Research of Anhui Medical University) for his guidance in performing TEM images.

Funding

This study was supported by the National Natural Science Foundation of China (81871785, 82073124 and 81672161).

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  1. Yu Kang and Qiangwei Li contributed equally to this work and share first authorship.

Authors and Affiliations

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

    Yu Kang, Rui Zhu, Shuang Li, Xin Xu & Zongsheng Yin

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

    Qiangwei Li & Xuanming Shi

  3. Department of Orthopedics, The Affiliated Chaohu Hospital of Anhui Medical University, Anhui Medical University, 64 Chaohu Northern Road, Hefei, 238001, China

    Rui Zhu & Zongsheng Yin

  4. The Key Laboratory of Microbiology and Parasitology of Anhui Province, Anhui Medical University, 81 Meishan Road, Hefei, 230032, China

    Shuang Li

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Contributions

Yu Kang, Xuanming Shi and Zongsheng Yin designed the study. Yu Kang and Qiangwei Li performed the animal experiments and bioinformatic analysis together with the help of Rui Zhu, Shuang Li, and Xin Xu. Rui Zhu performed HE, Nissl, and Perls-blue stain. Shuang Li performed the TEM test. Xin Xu performed the WB test. Yu Kang and Qiangwei Li wrote the manuscript. Rui Zhu, Shuang Li, and Xin Xu contributed to data analysis and figures. All authors reviewed and concurred with the final manuscript. Yu Kang and Zongsheng Yin took responsibility for the whole study.

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Correspondence to Xuanming Shi or Zongsheng Yin.

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The study protocols regarding the animals were approved by the Ethics Committee of Anhui Medical University of China (No.LLSC 20201135).

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Kang, Y., Li, Q., Zhu, R. et al. Identification of Ferroptotic Genes in Spinal Cord Injury at Different Time Points: Bioinformatics and Experimental Validation. Mol Neurobiol 59, 5766–5784 (2022). https://doi.org/10.1007/s12035-022-02935-y

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