Identification and validation of expression and functions of ferroptosis-related gene HILPDA in early-onset preeclampsia placentas
BackgroundEarly-onset preeclampsia (EOPE) is a severe form of preeclampsia that mainly contributes to maternal and perinatal morbidity and mortality worldwide. This study aimed to systematically analyze the expression and function of ferroptosis-related gene HILPDA in EOPE placentas.MethodsWe includ...
Saved in:
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2025-08-01
|
| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1627057/full |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849395997617160192 |
|---|---|
| author | Qianghua Wang Xuegu Wang Jiaojiao Fei Chuanyue Jiang Yafen Tao Nana Yang Huijuan Chen Chengli Dou Biao Ding Danli Du Xiang Li |
| author_facet | Qianghua Wang Xuegu Wang Jiaojiao Fei Chuanyue Jiang Yafen Tao Nana Yang Huijuan Chen Chengli Dou Biao Ding Danli Du Xiang Li |
| author_sort | Qianghua Wang |
| collection | DOAJ |
| description | BackgroundEarly-onset preeclampsia (EOPE) is a severe form of preeclampsia that mainly contributes to maternal and perinatal morbidity and mortality worldwide. This study aimed to systematically analyze the expression and function of ferroptosis-related gene HILPDA in EOPE placentas.MethodsWe included five transcriptomic datasets (GSE148241, GSE44711, GSE74341, GSE114691, GSE10588) downloaded from the Gene Expression Omnibus (GEO) in this study. Using differential expression analysis, weighted gene co-expression network analysis (WGCNA), and machine learning models (LASSO, SVM-RFE, Random Forest), We identified hub genes and diagnostic biomarkers. We performed functional enrichment (GO and KEGG) and immune infiltration analysis to elucidate molecular mechanisms. Experimental validation included Western blot on clinical placental samples and siRNA-mediated knockdown in HTR-8/SVneo trophoblasts to assess migration.ResultsWe observed HILPDA upregulation and confirmed its diagnostic accuracy (AUC=0.71) in EOPE placentas. Functional analysis revealed HILPDA-associated enrichment in immune regulation (leukocyte migration, MHC complexes) and cellular processes (collagen organization, HIF-1 signaling). Through WGCNA, we identified 171 HILPDA-associated DEGs. Machine learning prioritized PART1 as diagnostic biomarkers. Immune profiling highlighted HILPDA’s correlation with activated dendritic cells, neutrophils and resting mast cells. Experimentally, we confirmed HILPDA up-regulation in EOPE placentas and its critical role in suppressing trophoblast migration.ConclusionsOur study establishes HILPDA as a central mechanistic regulator involved in placental immune dysregulation and trophoblast migration in EOPE pathogenesis. The identified biomarkers PART1 and HILPDA-associated pathways may offer novel diagnostic and therapeutic targets for EOPE management, which contribute to reduce maternal morbidity and prevent perinatal mortality in this catastrophic pregnancy syndrome. |
| format | Article |
| id | doaj-art-54c452ab32cc4bff8b49fc6592f79a1e |
| institution | Kabale University |
| issn | 1664-3224 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj-art-54c452ab32cc4bff8b49fc6592f79a1e2025-08-20T03:39:28ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-08-011610.3389/fimmu.2025.16270571627057Identification and validation of expression and functions of ferroptosis-related gene HILPDA in early-onset preeclampsia placentasQianghua Wang0Xuegu Wang1Jiaojiao Fei2Chuanyue Jiang3Yafen Tao4Nana Yang5Huijuan Chen6Chengli Dou7Biao Ding8Danli Du9Xiang Li10Laboratory of Department of Infectious Diseases, First Affiliated Hospital of Bengbu Medical University, Bengbu, Anhui, ChinaReproductive Medicine Center, First Affiliated Hospital of Bengbu Medical University, Bengbu, Anhui, ChinaMolecular Diagnosis Center, Anhui Province Key Laboratory of Clinical and Preclinical Research in Respiratory Disease, First Affiliated Hospital of Bengbu Medical University, Bengbu, Anhui, ChinaReproductive Medicine Center, First Affiliated Hospital of Bengbu Medical University, Bengbu, Anhui, ChinaReproductive Medicine Center, First Affiliated Hospital of Bengbu Medical University, Bengbu, Anhui, ChinaReproductive Medicine Center, First Affiliated Hospital of Bengbu Medical University, Bengbu, Anhui, ChinaLaboratory of Department of Infectious Diseases, First Affiliated Hospital of Bengbu Medical University, Bengbu, Anhui, ChinaMolecular Diagnosis Center, Anhui Province Key Laboratory of Clinical and Preclinical Research in Respiratory Disease, First Affiliated Hospital of Bengbu Medical University, Bengbu, Anhui, ChinaReproductive Medicine Center, First Affiliated Hospital of Bengbu Medical University, Bengbu, Anhui, ChinaReproductive Medicine Center, First Affiliated Hospital of Bengbu Medical University, Bengbu, Anhui, ChinaMolecular Diagnosis Center, Anhui Province Key Laboratory of Clinical and Preclinical Research in Respiratory Disease, First Affiliated Hospital of Bengbu Medical University, Bengbu, Anhui, ChinaBackgroundEarly-onset preeclampsia (EOPE) is a severe form of preeclampsia that mainly contributes to maternal and perinatal morbidity and mortality worldwide. This study aimed to systematically analyze the expression and function of ferroptosis-related gene HILPDA in EOPE placentas.MethodsWe included five transcriptomic datasets (GSE148241, GSE44711, GSE74341, GSE114691, GSE10588) downloaded from the Gene Expression Omnibus (GEO) in this study. Using differential expression analysis, weighted gene co-expression network analysis (WGCNA), and machine learning models (LASSO, SVM-RFE, Random Forest), We identified hub genes and diagnostic biomarkers. We performed functional enrichment (GO and KEGG) and immune infiltration analysis to elucidate molecular mechanisms. Experimental validation included Western blot on clinical placental samples and siRNA-mediated knockdown in HTR-8/SVneo trophoblasts to assess migration.ResultsWe observed HILPDA upregulation and confirmed its diagnostic accuracy (AUC=0.71) in EOPE placentas. Functional analysis revealed HILPDA-associated enrichment in immune regulation (leukocyte migration, MHC complexes) and cellular processes (collagen organization, HIF-1 signaling). Through WGCNA, we identified 171 HILPDA-associated DEGs. Machine learning prioritized PART1 as diagnostic biomarkers. Immune profiling highlighted HILPDA’s correlation with activated dendritic cells, neutrophils and resting mast cells. Experimentally, we confirmed HILPDA up-regulation in EOPE placentas and its critical role in suppressing trophoblast migration.ConclusionsOur study establishes HILPDA as a central mechanistic regulator involved in placental immune dysregulation and trophoblast migration in EOPE pathogenesis. The identified biomarkers PART1 and HILPDA-associated pathways may offer novel diagnostic and therapeutic targets for EOPE management, which contribute to reduce maternal morbidity and prevent perinatal mortality in this catastrophic pregnancy syndrome.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1627057/fullearly-onset preeclampsiaHILPDAtrophoblast migrationimmune infiltrationferroptosis |
| spellingShingle | Qianghua Wang Xuegu Wang Jiaojiao Fei Chuanyue Jiang Yafen Tao Nana Yang Huijuan Chen Chengli Dou Biao Ding Danli Du Xiang Li Identification and validation of expression and functions of ferroptosis-related gene HILPDA in early-onset preeclampsia placentas Frontiers in Immunology early-onset preeclampsia HILPDA trophoblast migration immune infiltration ferroptosis |
| title | Identification and validation of expression and functions of ferroptosis-related gene HILPDA in early-onset preeclampsia placentas |
| title_full | Identification and validation of expression and functions of ferroptosis-related gene HILPDA in early-onset preeclampsia placentas |
| title_fullStr | Identification and validation of expression and functions of ferroptosis-related gene HILPDA in early-onset preeclampsia placentas |
| title_full_unstemmed | Identification and validation of expression and functions of ferroptosis-related gene HILPDA in early-onset preeclampsia placentas |
| title_short | Identification and validation of expression and functions of ferroptosis-related gene HILPDA in early-onset preeclampsia placentas |
| title_sort | identification and validation of expression and functions of ferroptosis related gene hilpda in early onset preeclampsia placentas |
| topic | early-onset preeclampsia HILPDA trophoblast migration immune infiltration ferroptosis |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1627057/full |
| work_keys_str_mv | AT qianghuawang identificationandvalidationofexpressionandfunctionsofferroptosisrelatedgenehilpdainearlyonsetpreeclampsiaplacentas AT xueguwang identificationandvalidationofexpressionandfunctionsofferroptosisrelatedgenehilpdainearlyonsetpreeclampsiaplacentas AT jiaojiaofei identificationandvalidationofexpressionandfunctionsofferroptosisrelatedgenehilpdainearlyonsetpreeclampsiaplacentas AT chuanyuejiang identificationandvalidationofexpressionandfunctionsofferroptosisrelatedgenehilpdainearlyonsetpreeclampsiaplacentas AT yafentao identificationandvalidationofexpressionandfunctionsofferroptosisrelatedgenehilpdainearlyonsetpreeclampsiaplacentas AT nanayang identificationandvalidationofexpressionandfunctionsofferroptosisrelatedgenehilpdainearlyonsetpreeclampsiaplacentas AT huijuanchen identificationandvalidationofexpressionandfunctionsofferroptosisrelatedgenehilpdainearlyonsetpreeclampsiaplacentas AT chenglidou identificationandvalidationofexpressionandfunctionsofferroptosisrelatedgenehilpdainearlyonsetpreeclampsiaplacentas AT biaoding identificationandvalidationofexpressionandfunctionsofferroptosisrelatedgenehilpdainearlyonsetpreeclampsiaplacentas AT danlidu identificationandvalidationofexpressionandfunctionsofferroptosisrelatedgenehilpdainearlyonsetpreeclampsiaplacentas AT xiangli identificationandvalidationofexpressionandfunctionsofferroptosisrelatedgenehilpdainearlyonsetpreeclampsiaplacentas |