Dysfunction of Decidual Macrophages Is a Potential Risk Factor in the Occurrence of Preeclampsia

Rong, Miaomiao; Yan, Xiang-Ping; Hong-ya, Zhang; Zhou, Chan; Zhang, Cong

doi:10.3389/fimmu.2021.655655

Cited by 14 publications

(12 citation statements)

References 68 publications

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“…PE has a great impact on growth and development of the fetus, impairs the structure and function of fetal cardiovascular system or kidney, and causes hypertension. 15 Current studies suggest that the pathogenesis of PE may be related to decidual macrophage dysfunction, 16 placental angiogenesis disorder, 17 placental aging, 18 , 19 protein aggregation, and defective placental aggregation phagocytosis. 20 At the molecular level, the microRNA spectrum of blood exosomes has been used to evaluate the pathophysiology of preeclampsia and predict the disease, 21 and there are more and more studies at gene level.…”

Section: Discussionmentioning

confidence: 99%

Gene Expression Network Analysis Identifies Potential Targets for Prevention of Preeclampsia

Yu¹,

Zhao²,

Sun³

et al. 2022

IJGM

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Objective Preeclampsia (PE) is a pregnancy-specific multisystem disease as well as an important cause of maternal and perinatal death. This study aimed to analyze the placental transcriptional data and clinical information of PE patients available in the published database and predict the target genes for prevention of PE. Methods The clinical information and corresponding RNA data of PE patients were downloaded from the GEO database. Cluster analysis was performed to examine the correlation between different genotyping genes and clinical manifestations. Then, bioinformatic approaches including GO, KEGG, WGCNA, and GSEA were employed to functionally characterize candidate target genes involved in pathogenesis of PE. Results Two PE datasets GSE60438 and GSE75010 were obtained and combined, thereby providing the data of 205 samples in total (100 non-PE and 105 PE samples). After eliminating the batch effect, we grouped and analyzed the integrated data, and further performed GSEA analysis. It was found that the genes in group 1 and group 2 were different from those in normal samples. Moreover, WGCNA analysis revealed that genes in group 1 were up-regulated in turquoise module, including SASH1 , PIK3CB and FLT-1 , while genes in group 2 were up-regulated in the blue and brown modules. We further conducted GO and KEGG pathway enrichment analyses and found that the differential genes in turquoise module were mainly involved in biological processes such as small molecular catabolic process, while being highly enriched in pathways, including MAPK signaling pathway and Rap1 signaling pathway. Conclusion FLT-1 was conventionally used to predict PE risk, and sFLT-1 could also be used as an indicator to evaluate PE treatment effect. As a candidate biomarker for predicting PE, SASH1 may participate in proliferation, migration, invasion and epithelial mesenchymal transformation of human trophoblast cells by regulating MAPK pathway and Rap1 signaling pathway, thus affecting the progression of PE. The mechanism allowing PIK3CB to regulate PE development was not clear, while the gene could be another candidate biomarker for PE risk prediction. This is an exploratory study and our findings were still required verification in further studies.

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Section: Discussionmentioning

confidence: 99%

Gene Expression Network Analysis Identifies Potential Targets for Prevention of Preeclampsia

Yu¹,

Zhao²,

Sun³

et al. 2022

IJGM

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“…More and more studies have shown that abnormal decidualization is an important factor leading to the occurrence of PE [27,36,37]. A large number of decidualization-related genes are abnormally expressed in the decidua of PE patients [38][39][40][41][42][43]. The transcriptional signatures that promote endometrial decidualization deficiency can be detected before or after pregnancy [28,44,45].…”

Section: Discussionmentioning

confidence: 99%

Establishment and validation of a predictive model of preeclampsia based on transcriptional signatures of 43 genes in decidua basalis and peripheral blood

Hong-ya

Zhang

et al. 2022

BMC Bioinformatics

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Preeclampsia (PE) has an increasing incidence worldwide, and there is no gold standard for prediction. Recent progress has shown that abnormal decidualization and impaired vascular remodeling are essential to PE pathogenesis. Therefore, it is of great significance to analyze the decidua basalis and blood changes of PE to explore new methods. Here, we performed weighted gene co-expression network analysis based on 9553 differentially expressed genes of decidua basalis data (GSE60438 includes 25 cases of PE and 23 non-cases) from Gene Expression Omnibus to screen relevant module-eigengenes (MEs). Among them, MEblue and MEgrey are the most correlated with PE, which contains 371 core genes. Subsequently, we applied the logistic least absolute shrinkage and selection operator regression, screened 43 genes most relevant to prediction from the intersections of the 371 genes and training set (GSE48424 includes 18 cases of PE and 18 non-cases) genes, and built a predictive model. The specificity and sensitivity are illustrated by receiver operating characteristic curves, and the stability was verified by two validation sets (GSE86200 includes 12 cases of PE and 48 non-cases, and GSE85307 includes 47 cases of PE and 110 non-cases). The results demonstrated that our predictive model shows good predictions, with an area under the curve of 0.991 for the training set, 0.874 and 0.986 for the validation sets. Finally, we found the 43 key marker genes in the model are closely associated with the clinically accepted predictive molecules, including FLT1, PIGF, ENG and VEGF. Therefore, this predictive model provides a potential approach for PE diagnosis and treatment.

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“…It has been indicated that CCR involved in modulating PE onset, 57,58 including early-onset HELLP syndrome 59 and early preeclampsia, 60 may be associated with mechanisms of regulating immune responses such as macrophages. 61 Furthermore, immune cells could contribute to preeclampsia pathogenesis through modulating inflammatory responses. 58 MHC class I plays an essential role in maternal-fetal immune balance.…”

Section: F I G U R E 5 Legend On Next Pagementioning

confidence: 99%

Comparison of immune‐related gene signatures and immune infiltration features in early‐ and late‐onset preeclampsia

Wu,

Ying,

et al. 2024

The Journal of Gene Medicine

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BackgroundPreeclampsia, a severe pregnancy syndrome, is widely accepted divided into early‐ and late‐onset preeclampsia (EOPE and LOPE) based on the onset time of preeclampsia, with distinct pathophysiological origins. However, the molecular mechanism especially immune‐related mechanisms for EOPE and LOPE is currently obscure. In the present study, we focused on placental immune alterations between EOPE and LOPE and search for immune‐related biomarkers that could potentially serve as potential therapeutic targets through bioinformatic analysis.MethodsThe gene expression profiling data was obtained from the Gene Expression Omnibus database. ESTIMATE algorithm and Gene Set Enrichment Analysis were employed to evaluate the immune status. The intersection of differentially expressed genes in GSE74341 series and immune‐related genes set screened differentially expressed immune‐related genes. Protein–protein interaction network and random forest were used to identify hub genes with a validation by a quantitative real‐time PCR. Kyoto Encyclopedia of Genes and Genomes pathways, Gene Ontology and gene set variation analysis were utilized to conduct biological function and pathway enrichment analyses. Single‐sample gene set enrichment analysis and CIBERSORTx tools were employed to calculate the immune cell infiltration score. Correlation analyses were evaluated by Pearson correlation analysis. Hub genes‐miRNA network was performed by the NetworkAnalyst online tool.ResultsImmune score and stromal score were all lower in EOPE samples. The immune system‐related gene set was significantly downregulated in EOPE compared to LOPE samples. Four hub differentially expressed immune‐related genes (IL15, GZMB, IL1B and CXCL12) were identified based on a protein–protein interaction network and random forest. Quantitative real‐time polymerase chain reaction validated the lower expression levels of four hub genes in EOPE compared to LOPE samples. Immune cell infiltration analysis found that innate and adaptive immune cells were apparent lacking in EOPE samples compared to LOPE samples. Cytokine‐cytokine receptor, para‐inflammation, major histocompatibility complex class I and T cell co‐stimulation pathways were significantly deficient and highly correlated with hub genes. We constructed a hub genes‐miRNA regulatory network, revealing the correlation between hub genes and hsa‐miR‐374a‐5p, hsa‐miR‐203a‐3p, hsa‐miR‐128‐3p, hsa‐miR‐155‐3p, hsa‐miR‐129‐2‐3p and hsa‐miR‐7‐5p.ConclusionsThe innate and adaptive immune systems were severely impaired in placentas of EOPE. Four immune‐related genes (IL15, GZMB, IL1B and CXCL12) were closely correlated with immune‐related pathogenesis of EOPE. The result of our study may provide a new basis for discriminating between EOPE and LOPE and acknowledging the role of the immune landscape in the eventual interference and tailored treatment of EOPE.

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Dysfunction of Decidual Macrophages Is a Potential Risk Factor in the Occurrence of Preeclampsia

Cited by 14 publications

References 68 publications

Gene Expression Network Analysis Identifies Potential Targets for Prevention of Preeclampsia

Gene Expression Network Analysis Identifies Potential Targets for Prevention of Preeclampsia

Establishment and validation of a predictive model of preeclampsia based on transcriptional signatures of 43 genes in decidua basalis and peripheral blood

Comparison of immune‐related gene signatures and immune infiltration features in early‐ and late‐onset preeclampsia

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