Min Zhang, Na Wei, Rong Lin, Yue Xu, Qingfu Zhang, Lina Jia, Xiaotong Zhang, Xiaojing Yang
{"title":"去铁胺解决代谢失调和尿路感染在体重相关妊娠糖尿病。","authors":"Min Zhang, Na Wei, Rong Lin, Yue Xu, Qingfu Zhang, Lina Jia, Xiaotong Zhang, Xiaojing Yang","doi":"10.1186/s40001-025-03013-4","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>The increasing prevalence of gestational diabetes mellitus (GDM), particularly among overweight or obese individuals, poses significant health risks. Excess iron contributes to oxidative stress, inflammation, and disruptions in immune and metabolic functions in GDM. Deferoxamine (DFO), an iron chelator, may offer a therapeutic solution by restoring immune and metabolic balance.</p><p><strong>Methods: </strong>We conducted a comprehensive multi-omics analysis using GEO transcriptomic data, applying Weighted Gene Co-expression Network Analysis (WGCNA) and gene set enrichment analysis to identify key immune-metabolic genes. Molecular docking experiments with DFO were performed using AutoDock Vina, and interactions were visualized in PyMOL. Various in vitro assays-CCK-8, qRT-PCR, Western blot, immunofluorescence, ELISA, and colony formation tests-were conducted under high glucose conditions to assess the effects of DFO, focusing on LAMA3 and the PI3K/AKT signaling pathway.</p><p><strong>Results: </strong>Key genes such as CDR2L, LIMCH1, LDLR, and LAMA3 were identified as being improperly regulated in cases of gestational diabetes mellitus (GDM). DFO demonstrated a significant affinity for these targets, especially LDLR. Functionally, DFO was found to improve cell survival during hyperglycemic stress, mitigate oxidative stress, and lower the concentrations of inflammatory cytokines like IL-6, IL-17, and IL-23. Notably, silencing or blocking LAMA3 reversed these effects, inhibiting the PI3K/AKT pathway, increasing apoptosis markers, and decreasing cell proliferation.</p><p><strong>Conclusions: </strong>DFO holds potential as a targeted treatment for GDM associated with obesity by addressing iron excess and immune-metabolic dysregulation. LAMA3 plays a crucial role in mediating DFO's anti-inflammatory and survival-promoting effects via the PI3K/AKT pathway. Further clinical studies are needed to explore DFO's therapeutic potential in GDM.</p>","PeriodicalId":11949,"journal":{"name":"European Journal of Medical Research","volume":"30 1","pages":"897"},"PeriodicalIF":3.4000,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12482621/pdf/","citationCount":"0","resultStr":"{\"title\":\"Deferoxamine addresses metabolic dysregulation and urinary tract infections in weight-associated gestational diabetes mellitus.\",\"authors\":\"Min Zhang, Na Wei, Rong Lin, Yue Xu, Qingfu Zhang, Lina Jia, Xiaotong Zhang, Xiaojing Yang\",\"doi\":\"10.1186/s40001-025-03013-4\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>The increasing prevalence of gestational diabetes mellitus (GDM), particularly among overweight or obese individuals, poses significant health risks. Excess iron contributes to oxidative stress, inflammation, and disruptions in immune and metabolic functions in GDM. Deferoxamine (DFO), an iron chelator, may offer a therapeutic solution by restoring immune and metabolic balance.</p><p><strong>Methods: </strong>We conducted a comprehensive multi-omics analysis using GEO transcriptomic data, applying Weighted Gene Co-expression Network Analysis (WGCNA) and gene set enrichment analysis to identify key immune-metabolic genes. Molecular docking experiments with DFO were performed using AutoDock Vina, and interactions were visualized in PyMOL. Various in vitro assays-CCK-8, qRT-PCR, Western blot, immunofluorescence, ELISA, and colony formation tests-were conducted under high glucose conditions to assess the effects of DFO, focusing on LAMA3 and the PI3K/AKT signaling pathway.</p><p><strong>Results: </strong>Key genes such as CDR2L, LIMCH1, LDLR, and LAMA3 were identified as being improperly regulated in cases of gestational diabetes mellitus (GDM). DFO demonstrated a significant affinity for these targets, especially LDLR. Functionally, DFO was found to improve cell survival during hyperglycemic stress, mitigate oxidative stress, and lower the concentrations of inflammatory cytokines like IL-6, IL-17, and IL-23. Notably, silencing or blocking LAMA3 reversed these effects, inhibiting the PI3K/AKT pathway, increasing apoptosis markers, and decreasing cell proliferation.</p><p><strong>Conclusions: </strong>DFO holds potential as a targeted treatment for GDM associated with obesity by addressing iron excess and immune-metabolic dysregulation. LAMA3 plays a crucial role in mediating DFO's anti-inflammatory and survival-promoting effects via the PI3K/AKT pathway. Further clinical studies are needed to explore DFO's therapeutic potential in GDM.</p>\",\"PeriodicalId\":11949,\"journal\":{\"name\":\"European Journal of Medical Research\",\"volume\":\"30 1\",\"pages\":\"897\"},\"PeriodicalIF\":3.4000,\"publicationDate\":\"2025-09-29\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12482621/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"European Journal of Medical Research\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1186/s40001-025-03013-4\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"MEDICINE, RESEARCH & EXPERIMENTAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"European Journal of Medical Research","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1186/s40001-025-03013-4","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"MEDICINE, RESEARCH & EXPERIMENTAL","Score":null,"Total":0}
Deferoxamine addresses metabolic dysregulation and urinary tract infections in weight-associated gestational diabetes mellitus.
Background: The increasing prevalence of gestational diabetes mellitus (GDM), particularly among overweight or obese individuals, poses significant health risks. Excess iron contributes to oxidative stress, inflammation, and disruptions in immune and metabolic functions in GDM. Deferoxamine (DFO), an iron chelator, may offer a therapeutic solution by restoring immune and metabolic balance.
Methods: We conducted a comprehensive multi-omics analysis using GEO transcriptomic data, applying Weighted Gene Co-expression Network Analysis (WGCNA) and gene set enrichment analysis to identify key immune-metabolic genes. Molecular docking experiments with DFO were performed using AutoDock Vina, and interactions were visualized in PyMOL. Various in vitro assays-CCK-8, qRT-PCR, Western blot, immunofluorescence, ELISA, and colony formation tests-were conducted under high glucose conditions to assess the effects of DFO, focusing on LAMA3 and the PI3K/AKT signaling pathway.
Results: Key genes such as CDR2L, LIMCH1, LDLR, and LAMA3 were identified as being improperly regulated in cases of gestational diabetes mellitus (GDM). DFO demonstrated a significant affinity for these targets, especially LDLR. Functionally, DFO was found to improve cell survival during hyperglycemic stress, mitigate oxidative stress, and lower the concentrations of inflammatory cytokines like IL-6, IL-17, and IL-23. Notably, silencing or blocking LAMA3 reversed these effects, inhibiting the PI3K/AKT pathway, increasing apoptosis markers, and decreasing cell proliferation.
Conclusions: DFO holds potential as a targeted treatment for GDM associated with obesity by addressing iron excess and immune-metabolic dysregulation. LAMA3 plays a crucial role in mediating DFO's anti-inflammatory and survival-promoting effects via the PI3K/AKT pathway. Further clinical studies are needed to explore DFO's therapeutic potential in GDM.
期刊介绍:
European Journal of Medical Research publishes translational and clinical research of international interest across all medical disciplines, enabling clinicians and other researchers to learn about developments and innovations within these disciplines and across the boundaries between disciplines. The journal publishes high quality research and reviews and aims to ensure that the results of all well-conducted research are published, regardless of their outcome.