• Chongjuan Yin, Yansu Ji, Ning Ma, Kai Chen, Wencheng Zhang, Dan Bai, Xiaojun Jia, Shihai Xia, and Huaiqing Yin.
• First Hospital of Shanxi Medical University, Taiyuan, Shanxi, China; Shanxi Medical University, Taiyuan, Shanxi, China.
• Neuroscience. 2022 Feb 10; 483: 52-65.

AbstractNeonatal hypoxic-ischemic brain damage (HIBD) is one of the main causes of neonatal acute death and chronic nervous system impairment, but still lacks effective treatments. ZNF580/ZFP580, reported in our previous studies, may be a newly identified member of the Krüppel-like factor (KLF) family, and has anti-apoptotic effects during ischemic myocardial injury. In the present study, we showed that the expression levels of both ZFP580/ZNF580 mRNA and protein increased significantly in neonatal HIBD rats and oxygen-glucose deprivation (OGD) SH-SY5Y cell models. ZNF580 overexpression promoted neuron survival and suppressed neuron apoptosis after OGD in neuron-like SH-SY5Y cells, while interference with ZNF580 resulted in the opposite results. RNA-seq analysis identified 248 differentially-expressed genes (DEGs) between ZNF580 overexpression SH-SY5Y cells and interference-expressed SH-SY5Y cells. Gene Ontology functional enrichment analysis showed that these DEGs played significant roles in the growth, development, and regeneration of axons, DNA biosynthetic processes, DNA replication, and apoptosis. Kyoto Encyclopedia of Genes and Genomes enrichment analysis indicated that these DEGs were found in some pathways, including ferroptosis, glutamatergic synapses, protein processing in the endoplasmic reticulum, estrogen signaling pathways, the TGF-beta signaling pathway, and the longevity regulating pathway. The qRT-PCR validation results were consistent with RNA-seq results, which showed that HSPA5, IGFBP3, NTN4, and KLF9 increased in ZNF580-overexpressed SH-SY5Y cells and decreased in interference-expressed SH-SY5Y cells, when compared with normal cells. Together, the results suggested that ZNF580 targeted these genes to inhibit neuronal apoptosis.Copyright © 2021 IBRO. Published by Elsevier Ltd. All rights reserved.

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