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ORIGINAL RESEARCH article

Front. Endocrinol.
Sec. Diabetes: Molecular Mechanisms
Volume 15 - 2024 | doi: 10.3389/fendo.2024.1437979
This article is part of the Research Topic Understanding and Managing Diabetic Neuropathy: Current Perspectives and Future Directions View all 5 articles

Identification of key genes and immune infiltration of diabetic peripheral neuropathy in mice and human based on bioinformatics analysis

Provisionally accepted
  • 1 Division of Geriatric Endocrinology, Department of Geriatrics, First Affiliated Hospital, Nanjing Medical University, Nanjing, Liaoning Province, China
  • 2 First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China

The final, formatted version of the article will be published soon.

    Background: Diabetic peripheral neuropathy (DPN) is a common chronic complication of diabetes, while the underlying molecular mechanisms are still unclear. This study aimed to screen the key genes and the roles of immune infiltration in DPN using bioinformatics analysis. Methods: DPN mice datasets including GSE222778, GSE11343, GSE70852, GSE27382, and GSE34889 were retrieved from the GEO database. Data of human DPN were retrieved from the dbGaP. The differentially expressed genes (DEGs) were selected and further analyzed by using the Gene Ontology, Kyoto Encyclopedia of Genes and Genomes enrichment analysis, and Gene Set Enrichment analysis (GSEA) to find the shared key pathway. Protein-protein interaction networks were built in shared mice and human DEGs. The hub genes were selected and verified in vitro using high-glucose treated PC12 cells and Schwann cells. The single-sample GSEA (ssGSEA) algorithm was used to analyze the proportions of infiltrating immune cells in human DPN and the subsequent correlations with hub genes. Results: A total of 323 mice DEGs and 501 human DEGs were selected, and they were found significantly enriched in immune-related biological functions and pathways. Total 13 DEGs were found shared in mice and human DPN datasets, and among them there were 7 hub genes including PLAUR, S100A8, IL7R, CXCL13, SRPX2, CD300LB, and CFI. The expression of Cfi, S100a8, Cxcl13 and Cd300lb were consistently confirmed in vitro. The scores of Neutrophils and NK CD56bright cells varied most significantly by immune cell infiltration analysis (P<0.01). Besides the selected hub genes were found highly correlated with the immune infiltration. Conclusion: Our study indicated the importance of immune dysregulations in DPN and identified several hub genes through combined analysis in mice and human DPN samples, thus providing potential diagnostic and therapeutic targets in the future.

    Keywords: Diabetic peripheral neuropathy, Bioinformatics analysis, Differentially expressed genes, Hub genes, Immune infiltration

    Received: 24 May 2024; Accepted: 23 Oct 2024.

    Copyright: © 2024 Zhang, Zhou, Liu and Zhou. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    Juan Liu, Division of Geriatric Endocrinology, Department of Geriatrics, First Affiliated Hospital, Nanjing Medical University, Nanjing, 210029, Liaoning Province, China
    Nan Zhou, First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan Province, China

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.