Ferroptosis and its potential role in gestational diabetes mellitus: updated evidence from pathogenesis to therapy
Yan Zhao,
Qianqian Gao,
Baoxuan Li
et al.
Abstract:BackgroundStudies have demonstrated that high iron status is positively associated with gestational diabetes mellitus (GDM), implying that iron overload and ferroptosis play important roles in the development of GDM. The aim of this study was to explore effective therapeutic drugs from traditional Chinese medicine (TCM)formulas for the treatment of GDM based on ferroptosis.MethodsIn this study, the presence of ferroptosis in the placenta was verified through clinical and experimental data, and key genes were s… Show more
“… 14 Recently, there has been emerging evidence supporting the involvement of ferroptosis in patients with gestational diabetes mellitus (GDM) and the possible modulatory roles of ferroptosis-related genes in the molecular mechanisms of GDM. 15 Yifang Zheng et al found that correcting the imbalance of fatty acid oxidation/peroxide-induced ferroptosis could ameliorate placental injury in GDM. 16 Studies have also suggested that targeting ferroptosis may be a potential therapeutic approach for treating GDM.…”
Purpose
Gestational diabetes mellitus (GDM) is a common metabolic disorder during pregnancy that is associated with placental inflammation and adverse pregnancy outcomes. However, the mechanisms of inflammation in GDM are still unclear.
Methods
Bulk transcriptome, single-cell transcriptome, clinical information, and samples were collected from GSE154414, GSE70493, GSE173193 and a retrospective cohort. Bioinformatics prediction was used to explore the mechanisms of placental inflammation, and multiplex immunofluorescence was used to validate the results.
Results
First, we found that GDM is characterized by low-grade inflammation and is linked to several adverse pregnancy outcomes, as supported by our collected clinical data. Additionally, we identified ten hub genes (
FCGR3B, CXCR1, MMP9, ITGAX, CCL5, GZMB, S100A8, LCN2, TGFB1
, and
LTF
) as potential therapy targets and confirmed the binding of corresponding predictive therapeutic agents by molecular docking. Transcriptome sequencing analysis has shown that macrophages are primarily responsible for the emergence of placental inflammation, and that M1 macrophage polarization increased while M2 macrophage polarization decreased in GDM when compared to the control sample. Multiplex immunofluorescence staining of CD68, CD80, and ACSL4 was performed and suggested that ferroptosis of macrophages may contribute to placental inflammation in GDM.
Conclusion
In conclusion, our findings provide a better understanding of the mechanisms of inflammation in GDM and suggest potential therapeutic targets for this condition.
“… 14 Recently, there has been emerging evidence supporting the involvement of ferroptosis in patients with gestational diabetes mellitus (GDM) and the possible modulatory roles of ferroptosis-related genes in the molecular mechanisms of GDM. 15 Yifang Zheng et al found that correcting the imbalance of fatty acid oxidation/peroxide-induced ferroptosis could ameliorate placental injury in GDM. 16 Studies have also suggested that targeting ferroptosis may be a potential therapeutic approach for treating GDM.…”
Purpose
Gestational diabetes mellitus (GDM) is a common metabolic disorder during pregnancy that is associated with placental inflammation and adverse pregnancy outcomes. However, the mechanisms of inflammation in GDM are still unclear.
Methods
Bulk transcriptome, single-cell transcriptome, clinical information, and samples were collected from GSE154414, GSE70493, GSE173193 and a retrospective cohort. Bioinformatics prediction was used to explore the mechanisms of placental inflammation, and multiplex immunofluorescence was used to validate the results.
Results
First, we found that GDM is characterized by low-grade inflammation and is linked to several adverse pregnancy outcomes, as supported by our collected clinical data. Additionally, we identified ten hub genes (
FCGR3B, CXCR1, MMP9, ITGAX, CCL5, GZMB, S100A8, LCN2, TGFB1
, and
LTF
) as potential therapy targets and confirmed the binding of corresponding predictive therapeutic agents by molecular docking. Transcriptome sequencing analysis has shown that macrophages are primarily responsible for the emergence of placental inflammation, and that M1 macrophage polarization increased while M2 macrophage polarization decreased in GDM when compared to the control sample. Multiplex immunofluorescence staining of CD68, CD80, and ACSL4 was performed and suggested that ferroptosis of macrophages may contribute to placental inflammation in GDM.
Conclusion
In conclusion, our findings provide a better understanding of the mechanisms of inflammation in GDM and suggest potential therapeutic targets for this condition.
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