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Identification of CCL20 as a Key Biomarker of Inflammatory Responses in the Pathogenesis of Intracerebral Hemorrhage

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Abstract

Inflammatory responses after intracerebral hemorrhage (ICH) contribute to severe secondary brain injury, leading to poor clinical outcomes. However, the responsible genes for effective anti-inflammation treatment in ICH remain poorly elucidated. The differentially expressed genes (DEGs) of human ICH were explored by online GEO2R. Go and KEGG were used to explore the biological function of DEGs. Protein–protein interactions (PPI) were built in the String database. Critical modules of PPI were identified by a molecular complex detection algorithm (MCODE). Cytohubba was used to determine the hub genes. The mRNA-miRNA interaction network was built in the miRWalk database. The rat ICH model was applied to validate the key genes. A total of 776 DEGs were identified in ICH. Go and KEGG analyses indicated that DEGs were mainly involved in neutrophil activation and the TNF signaling pathway. GSEA analysis presented that DEGs were significantly enriched in TNF signaling and inflammatory response. PPI network was constructed in the 48 differentially expressed inflammatory response-related genes. The critical module of the PPI network was constructed by 7 MCODE genes and functioned as the inflammatory response. The top 10 hub genes with the highest degrees were identified in the inflammatory response after ICH. CCL20 was confirmed as a key gene and mainly expressed in neurons in the rat ICH model. The regulatory network between CCL20 and miR-766 was built, and the miR-766 decrease was confirmed in a human ICH dataset. CCL20 is a key biomarker of inflammatory response after intracerebral hemorrhage, providing a potential target for inflammatory intervention in ICH.

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Data Availability

All the datasets that support the findings of this study are available from the Gene Expression Omnibus at http://www.ncbi.nlm.nih.gov/geo/, including GSE24265, GSE171144, and GSE43618 series.

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Funding

This work was supported by the Chinese Government Scholarship from the Chinese scholarship council (CSC NO.202206920038).

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Author notes

  1. Zong-Qing Zheng and Gui-Qiang Yuan contributed equally to this work.

Authors and Affiliations

  1. Department of Neurosurgery & Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, 188 Shizi Street, Suzhou, Jiangsu Province, 215006, China

    Zong-Qing Zheng, Guo-Guo Zhang & Zhong Wang

  2. Beijing Neurosurgical Institute & Department of Neurosurgery, Beijing Tiantan Hospital Affiliated to Capital Medical University, Capital Medical University, Beijing, China

    Gui-Qiang Yuan

  3. Department of Neurology & Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, Jiangsu Province, Suzhou, China

    Yan-Ting Chen & Qian-Qian Nie

Authors
  1. Zong-Qing Zheng
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  2. Gui-Qiang Yuan
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  6. Zhong Wang
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Contributions

Zhong Wang performed the study concept and design; Zong-Qing Zheng and Gui-Qiang Yuan performed most of the experiments and bioinformatic analysis; Zong-Qing Zheng and Gui-Qiang Yuan provided acquisition, analysis, and interpretation of data and statistical analysis; Guo-Guo Zhang, Yan-Ting Chen, and Qian-Qian Nie provided technical and material support. Zong-Qing Zheng and Gui-Qiang Yuan conducted the writing, review, and revision of the paper; Zhong Wang supervised the project. All authors read and approved the final paper.

Corresponding author

Correspondence to Zhong Wang.

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Animal experiments were conducted following the National Research Council’s Guide for the Care and Use of Laboratory Animals. The experimental protocols were approved by the Ethics Committee of the First Affiliated Hospital of Soochow University.

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Zheng, ZQ., Yuan, GQ., Zhang, GG. et al. Identification of CCL20 as a Key Biomarker of Inflammatory Responses in the Pathogenesis of Intracerebral Hemorrhage. Inflammation 46, 1290–1304 (2023). https://doi.org/10.1007/s10753-023-01807-4

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  • DOI: https://doi.org/10.1007/s10753-023-01807-4

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