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ORIGINAL RESEARCH article

Front. Mol. Biosci.
Sec. Molecular Diagnostics and Therapeutics
Volume 11 - 2024 | doi: 10.3389/fmolb.2024.1427352

Revealing the Regulation of Allergic Asthma Airway Epithelial Cell Inflammation by STEAP4 Targeting MIF through Machine Learning Algorithms and Single-cell Sequencing Analysis

Provisionally accepted
Lu Qiao Lu Qiao 1Shi-meng Li Shi-meng Li 2*Jun-nian Liu Jun-nian Liu 1*Hong-lei Duan Hong-lei Duan 3*Xiao-feng Jiang Xiao-feng Jiang 1*
  • 1 Department of Clinical Laboratory, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, Jilin Province, China
  • 2 Department of Clinical Laboratory, China-Japan Union Hospital, Jilin University, Changchun, Jilin Province, China
  • 3 Department of Digestive, China-Japan Union Hospital of Jilin University, Changchun, China

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

    Asthma comprises one of the most common chronic inflammatory conditions, yet still lacks effective diagnostic markers and treatment targets. To gain deeper insights, we comprehensively analyzed microarray datasets of airway epithelial samples from asthmatic patients and healthy subjects in the GEO database using three machine learning algorithms. Our investigation identified a pivotal gene, STEAP4. The expression of STEAP4 in patients with allergic asthma was found to be reduced. Furthermore, it was found to negatively correlate with the severity of the disease and was subsequently validated in asthmatic mice in this study. A ROC analysis of STEAP4 showed the AUC value was greater than 0.75. Functional enrichment analysis of STEAP4 indicated a strong correlation with IL-17, steroid hormone biosynthesis, and ferroptosis signaling pathways. Subsequently, intercellular communication analysis was performed using single-cell RNA sequencing data obtained from airway epithelial cells. The results revealed that samples exhibiting low levels of STEAP4 expression had a richer MIF signaling pathway in comparison to samples with high STEAP4 expression. Through both in vitro and in vivo experiments, we further confirmed the overexpression of STEAP4 in airway epithelial cells resulted in decreased expression of MIF, which in turn caused a decrease in the levels of the cytokines IL-33, IL-25, and IL-4; In contrast, when the STEAP4 was suppressed in airway epithelial cells, there was an upregulation of MIF expression, resulting in elevated levels of the cytokines IL-33, IL-25, and IL-4. These findings suggest that STEAP4 in the airway epithelium reduces allergic asthma Th2-type inflammatory reactions by inhibiting the MIF signaling pathway.

    Keywords: Allergic Asthma, airway epithelial cells, machine learning algorithms, Steap4, MIF

    Received: 03 May 2024; Accepted: 23 Jul 2024.

    Copyright: © 2024 Qiao, Li, Liu, Duan and Jiang. 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:
    Shi-meng Li, Department of Clinical Laboratory, China-Japan Union Hospital, Jilin University, Changchun, Jilin Province, China
    Jun-nian Liu, Department of Clinical Laboratory, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, Jilin Province, China
    Hong-lei Duan, Department of Digestive, China-Japan Union Hospital of Jilin University, Changchun, China
    Xiao-feng Jiang, Department of Clinical Laboratory, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, Jilin 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.