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miR-21 protects neonatal rats from hypoxic-ischemic brain damage by targeting CCL3

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Abstract

Hypoxic-ischemic brain damage (HIBD) represents one of the leading causes of neonatal mortality and permanent neurological disability worldwide. Compelling studies have identified implication of microRNAs (miRNAs) in HIBD. However, the molecular mechanism of miR-21 underlying the disease pathogenesis is unknown. The present study aims to explore the role of miR-21 in neonatal rats with HIBD. HIBD rat models were developed by carotid artery ligation and hypoxia treatment, and in vitro cell models were induced by oxygen–glucose deprivation. Through RT-qPCR and western blot analysis, high expression of CCL3 and poor expression of miR-21 were detected in brain tissues of rats with HIBD. Results of dual-luciferase reporter gene assay demonstrated that miR-21 could target and downregulate CCL3. The effect of miR-21 on the neurobehavioral ability of rats, the pathological characteristics of brain tissues, neuron apoptosis and as well as its impact on the NF-κB signaling pathway-related factors was examined by gain- and loss-of-function experiments. The obtained data suggested that upregulation of miR-21 resulted in significantly reduced cerebral infarct volume and degree of brain tissue damage, and improved neurobehavioral ability and memory ability in rats with HIBD through downregulation of CCL3. Besides, overexpression of miR-21 downregulated CCL3 to repress IKKα/β and p65 phosphorylation both in vivo and in vitro, hence disrupting the NF-κB signaling pathway. Taken together, the key findings of the current study underlie the cerebral protective effect of miR-21 against HIBD in neonatal rats through the inhibition of CCL3.

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Acknowledgements

We would like to give our sincere appreciation to the reviewers for their helpful comments on this article.

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Authors and Affiliations

  1. Outpatient Department of Pediatrics, The First Hospital of Jilin University, No. 1, Xinmin Street, Changchun, 130021, Jilin Province, People’s Republic of China

    Jiangtao Liu, Sai Zhang, Yuanyuan Huang & Liqun Sun

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  1. Jiangtao Liu
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  2. Sai Zhang
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  4. Liqun Sun
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Contributions

JL, SZ, YH and LS designed the study. JL and SZ collated the data, carried out data analyses and produced the initial draft of the manuscript. YH and LS contributed to drafting the manuscript. All authors have read and approved the final submitted manuscript.

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Correspondence to Liqun Sun.

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Liu, J., Zhang, S., Huang, Y. et al. miR-21 protects neonatal rats from hypoxic-ischemic brain damage by targeting CCL3. Apoptosis 25, 275–289 (2020). https://doi.org/10.1007/s10495-020-01596-3

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