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The Role of Cystathionine-β-Synthase, H2S, and miRNA-377 in Hypoxic-Ischemic Encephalopathy: Insights from Human and Animal Studies

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Abstract

We aimed to investigate the mechanism underlying the roles of miRNA-377, Cystathionine-β-synthase (CBS), and hydrogen sulfide (H2S) in the development of hypoxic-ischemic encephalopathy (HIE). We investigated the relationship between CBS, H2S, and miR-377 in both humans with HIE and animals with hypoxic-ischemic insult. An animal model of fetal rats with hypoxic-ischemic brain injury was established, and the fetal rats were randomly assigned to control and hypoxic-ischemic groups for 15 min (mild) and 30 min (moderate) groups. Human samples were collected from children diagnosed with HIE. Healthy or non-neurological disease children were selected as the control group. Hematoxylin–eosin (HE) staining, quantitative real-time polymerase chain reaction (qRT-PCR), enzyme-linked immunosorbent assay (ELISA), and western blot were used to conduct this study. Hypoxia–ischemia induced pathological alterations in brain tissue changes were more severe in groups with severe hypoxic insult. miRNA-377 expression levels were upregulated in brain tissue and serum of fetal rats and human samples with HIE compared to controls. Conversely, CBS and H2S expression levels were significantly decreased in both human and animal samples compared to controls. Our findings suggest that CBS is a target gene of miR-377 which may contribute to the development of HIE by regulating CBS/H2S. H2S has a protective effect against hypoxic damage in brain tissue. The study provides new insights into the potential mechanisms underlying the protective role of H2S in hypoxic brain damage and may contribute to the development of novel therapies for HIE.

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All data generated or analyzed during this study are included in this article.

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Funding

This work was supported by the Scientific Research Fund of Heilongjiang Provincial Education Department (No. 2019-KYYWF-1337) and the Construction Project of the Excellent Innovation Team for Basic Scientific Research Business Fee of Heilongjiang Provincial Universities (No. 2022-KYYWF-0652).

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Author notes

  1. Chun-Yang Liu and Hisham Al-Ward contributed equally to this work.

Authors and Affiliations

  1. School of Medicine, AnKang University, Ankang, Shanxi Province, China

    Chun-Yang Liu

  2. School of Medicine, Shanghai Institute of Stem Cell Research and Clinical Translation, Shanghai East Hospital, Tongji University, Shanghai, China

    Hisham Al-Ward, Wei Chen, Wenxia Gao, Chunxue Zhang, Orion Fan & Yi Eve Sun

  3. Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Jiamusi University, Jiamusi, China

    Ning Liu & Hui Xu

  4. Hainan University, Hainan Province, Haikou, China

    Francine Ngaffo Mekontso

  5. Department of Clinical Laboratory, Shanghai 10Th People’s Hospital of Tongji, University, Shanghai, China

    Abduh Murshed

  6. Huashan Hospital, Fudan University, Shanghai, China

    Zi-Rui Yu

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  1. Chun-Yang Liu
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Contributions

C-Y. L and H.A. managed the laboratory experiments; F.N.M. participated in the software; Z.R.Y and N.L. participated in western blot experiments; H. A wrote the paper; A.M. revised the paper; L. S., M.A., and O.F. proofread the manuscript; and Y.E.S and X.H. proofread and supervised the manuscript. All authors read and approved the final manuscript.

Corresponding authors

Correspondence to Yi Eve Sun or Hui Xu.

Ethics declarations

Ethical Approval and Consent to Participate

The study was conducted in accordance with the ethical standards of the Institutional Research Committee and the 1964 Helsinki Declaration and its subsequent amendments or comparable ethical standards. Informed verbal consent was obtained from the parents of all participants, and approved by Jiamusi University (JD10011). The animal study was approved by the Research Ethics Committee of Jiamusi University (SYK (Hei) 2016–014). The study procedures were conducted following the guidelines of the Chinese Ministry of Science and Technology.

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The authors declare no competing interests.

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Liu, CY., Al-Ward, H., Liu, N. et al. The Role of Cystathionine-β-Synthase, H2S, and miRNA-377 in Hypoxic-Ischemic Encephalopathy: Insights from Human and Animal Studies. J Mol Neurosci 73, 921–931 (2023). https://doi.org/10.1007/s12031-023-02165-4

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