Ferroptosis and its potential role in gestational diabetes mellitus: updated evidence from pathogenesis to therapy
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 C...
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| Format: | Article |
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Frontiers Media S.A.
2023-08-01
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| Series: | Frontiers in Endocrinology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fendo.2023.1177547/full |
| _version_ | 1797741286703235072 |
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| author | Yan Zhao Qianqian Gao Baoxuan Li Yang Wang Yue Wang |
| author_facet | Yan Zhao Qianqian Gao Baoxuan Li Yang Wang Yue Wang |
| author_sort | Yan Zhao |
| collection | DOAJ |
| description | 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 subsequently screened for association with ferroptosis in the development of GDM. The analysis was based on transcriptome sequencing of datasets combined with differentially expressed genes (DEGs) analysis and weighted gene correlation network analysis (WGCNA); functional enrichment analysis was also performed. A protein−protein interaction (PPI) network was constructed and pivotal genes were identified using Cytoscape. Finally, traditional Chinese medicine (TCM)formulas related to treating GDM were collected, then the proteins corresponding to the key genes were molecularly docked with the small molecular structures of clinically proven effective herbal tonics, and molecular dynamic simulations were performed to select the best candidates for pharmacological compounds.ResultsElevated ferritin levels in patients with GDM were verified using clinical data. The presence of ferroptosis in placental tissues of patients with GDM was confirmed using electron microscopy and western blotting. Ninety-nine key genes with the highest correlation with ferroptosis were identified from DEGs and weighted gene co-expression network analysis (WGCNA). Analysis using the Kyoto Encyclopedia of Genes and Genomes demonstrated that the DEGs were primarily involved in the oxidative phosphorylation pathway. The key genes were further screened by PPI; two key genes, SF3B14 and BABAM1, were identified by combining the gene corresponding to protein structure and function, followed by molecular docking and molecular dynamic simulation. Coptis chinensis was proposed as the best candidate for herbal treatment at the molecular level.ConclusionThis data revealed the presence of ferroptosis in patients with GDM and identified possible modulatory roles of ferroptosis-related genes involved in the molecular mechanisms of GDM, providing new insights into the pathogenesis of GDM, which also provided new directions for the systematic optimization of TCM formulas for the management and targeted treatment of GDM. |
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| format | Article |
| id | doaj.art-bbcf0007aa624951ac87c320123bab37 |
| institution | Directory Open Access Journal |
| issn | 1664-2392 |
| language | English |
| last_indexed | 2024-03-12T14:24:37Z |
| publishDate | 2023-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Endocrinology |
| spelling | doaj.art-bbcf0007aa624951ac87c320123bab372023-08-18T11:36:56ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922023-08-011410.3389/fendo.2023.11775471177547Ferroptosis and its potential role in gestational diabetes mellitus: updated evidence from pathogenesis to therapyYan Zhao0Qianqian Gao1Baoxuan Li2Yang Wang3Yue Wang4Department of Obstetrics and Gynaecology, Shengjing Hospital of China Medical University, Shenyang, Liaoning, ChinaDepartment of Obstetrics, Weifang People’s Hospital, Weifang, ShanDong, ChinaDepartment of Obstetrics and Gynaecology, Shengjing Hospital of China Medical University, Shenyang, Liaoning, ChinaDepartment of Obstetrics and Gynaecology, Shengjing Hospital of China Medical University, Shenyang, Liaoning, ChinaDepartment of Obstetrics and Gynaecology, Shengjing Hospital of China Medical University, Shenyang, Liaoning, ChinaBackgroundStudies 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 subsequently screened for association with ferroptosis in the development of GDM. The analysis was based on transcriptome sequencing of datasets combined with differentially expressed genes (DEGs) analysis and weighted gene correlation network analysis (WGCNA); functional enrichment analysis was also performed. A protein−protein interaction (PPI) network was constructed and pivotal genes were identified using Cytoscape. Finally, traditional Chinese medicine (TCM)formulas related to treating GDM were collected, then the proteins corresponding to the key genes were molecularly docked with the small molecular structures of clinically proven effective herbal tonics, and molecular dynamic simulations were performed to select the best candidates for pharmacological compounds.ResultsElevated ferritin levels in patients with GDM were verified using clinical data. The presence of ferroptosis in placental tissues of patients with GDM was confirmed using electron microscopy and western blotting. Ninety-nine key genes with the highest correlation with ferroptosis were identified from DEGs and weighted gene co-expression network analysis (WGCNA). Analysis using the Kyoto Encyclopedia of Genes and Genomes demonstrated that the DEGs were primarily involved in the oxidative phosphorylation pathway. The key genes were further screened by PPI; two key genes, SF3B14 and BABAM1, were identified by combining the gene corresponding to protein structure and function, followed by molecular docking and molecular dynamic simulation. Coptis chinensis was proposed as the best candidate for herbal treatment at the molecular level.ConclusionThis data revealed the presence of ferroptosis in patients with GDM and identified possible modulatory roles of ferroptosis-related genes involved in the molecular mechanisms of GDM, providing new insights into the pathogenesis of GDM, which also provided new directions for the systematic optimization of TCM formulas for the management and targeted treatment of GDM.https://www.frontiersin.org/articles/10.3389/fendo.2023.1177547/fullgestational diabetes mellitusferroptosisbioinformaticWGCNAmolecular dockingmolecular dynamic simulation |
| spellingShingle | Yan Zhao Qianqian Gao Baoxuan Li Yang Wang Yue Wang Ferroptosis and its potential role in gestational diabetes mellitus: updated evidence from pathogenesis to therapy Frontiers in Endocrinology gestational diabetes mellitus ferroptosis bioinformatic WGCNA molecular docking molecular dynamic simulation |
| title | Ferroptosis and its potential role in gestational diabetes mellitus: updated evidence from pathogenesis to therapy |
| title_full | Ferroptosis and its potential role in gestational diabetes mellitus: updated evidence from pathogenesis to therapy |
| title_fullStr | Ferroptosis and its potential role in gestational diabetes mellitus: updated evidence from pathogenesis to therapy |
| title_full_unstemmed | Ferroptosis and its potential role in gestational diabetes mellitus: updated evidence from pathogenesis to therapy |
| title_short | Ferroptosis and its potential role in gestational diabetes mellitus: updated evidence from pathogenesis to therapy |
| title_sort | ferroptosis and its potential role in gestational diabetes mellitus updated evidence from pathogenesis to therapy |
| topic | gestational diabetes mellitus ferroptosis bioinformatic WGCNA molecular docking molecular dynamic simulation |
| url | https://www.frontiersin.org/articles/10.3389/fendo.2023.1177547/full |
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