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Investigating the Potential Mechanisms of Ferroptosis and Autophagy in the Pathogenesis of Gestational Diabetes

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Abstract

Ferroptosis and autophagy are two different cellular processes that have recently been highlighted for their potential roles in the pathogenesis and progression of gestational diabetes (GD). This research sought to uncover the crucial genes tied to ferroptosis and autophagy in GD, further investigating their mechanisms. Differentially expressed genes (DEGs) linked to ferroptosis and autophagy in GD were identified using publicly available data. Pathway enrichment, protein interactions, correlation with immune cell infiltration, and diagnostic value of DEGs were analyzed. HTR-8/SVneo cells were subjected to varying glucose levels to evaluate cell viability and the expression of markers related to ferroptosis and proteins associated with autophagy. Crucial DEGs were validated in vitro. A total of 12 DEGs associated with ferroptosis and autophagy in GD were identified, enriched in the PI3K-AKT signaling pathway. These genes exhibited significant correlations with monocyte infiltration, resting CD4 memory T cells, and follicular helper T cells. They exhibited high diagnostic value for GD (AUC: 0.77–0.97). High glucose treatment inhibited cell viability, induced ferroptosis, and activated autophagy in HTR-8/SVneo cells. Validation confirmed altered expression of SNCA, MTDH, HMGB1, TLR4, SOX2, SESN2, and HMOX1 after glucose treatments. In conclusion, ferroptosis and autophagy may play a role in GD development through key genes (e.g., TLR4, SOX2, SNCA, HMOX1, HMGB1). These genes could serve as promising biomarkers for GD diagnosis.

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Data Availability

The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.

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Author contributions

Conceptualization, writing–original draft, methodology and formal analysis: Xiaomei Lv; Formal analysis, investigation, resources and visualization: Jing Jiang; Conceptualization, visualization, project administration and writing–review & editing: Yujun An. All authors have read and approved the final manuscript.

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The authors did not receive support from any organization for the submitted work.

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Authors and Affiliations

  1. Department of Obstetrics, Central Hospital Affiliated to Shandong First Medical University, Jinan, 250013, China

    Xiaomei Lv & Yujun An

  2. Department of Obstetrics, The Fourth people’s hospital of Jinan, Jinan, 250031, China

    Jing Jiang

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  1. Xiaomei Lv
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Correspondence to Yujun An.

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Lv, X., Jiang, J. & An, Y. Investigating the Potential Mechanisms of Ferroptosis and Autophagy in the Pathogenesis of Gestational Diabetes. Cell Biochem Biophys 82, 279–290 (2024). https://doi.org/10.1007/s12013-023-01196-3

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  • DOI: https://doi.org/10.1007/s12013-023-01196-3

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