Differential Methylation in Promoter Regions of the Genes NR3C1 and HSP90AA1, Involved in the Regulation, and Bioavailability of Cortisol in Leukocytes of Women With Preeclampsia

Torres-Salazar, Quitzia Libertad; Martínez-López, Yolanda; Reyes-Romero, Miguel Arturo; Pérez‐Morales, Rebeca; Sifuentes-Álvarez, Antonio; Salvador-Moysén, Jaime

doi:10.3389/fmed.2020.00206

Cited by 8 publications

(6 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…And we also identified that the acetylation level of K209 on HSP90AA1 was increased in the GDM placentas. In addition, one study of DNA methylation found differential methylation of HSP90AA1 may have a regulatory role in response to stress for women with PE [34]. We identified that the acetylation level of K292 on HSP90AA1 was increased in PE placental tissues.…”

Section: Discussionmentioning

confidence: 76%

Integrated proteome and acetylome analyses unveil protein features of gestational diabetes mellitus and preeclampsia

Tang

et al. 2022

Proteomics

View full text Add to dashboard Cite

Gestational diabetes mellitus (GDM) and preeclampsia (PE) are associated with maternal and infant health. Although the pathogenesis of PE and GDM remains controversial, oxidative stress is involved in the underlying pathology of GDM and PE. Protein lysine acetylation (Kac) plays an important regulatory role in biological processes. There is little data regarding the association of the maternal acetylome with GDM and PE. This study aimed to assess the potential value of the proteome and acetylome for GDM and PE. In our study, we included placental tissues from healthy individuals (n = 6), GDM patients (n = 6), and PE patients (n = 6) to perform 4D-label free quantification proteomics analysis and PRM analysis. We identified 22 significantly regulated proteins and 192 significantly regulated acetylated proteins between the GDM and PE groups. Furthermore, 192 significantly regulated acetylated proteins were mainly enriched in endoplasmic reticulum stress (ERS) and ferroptosis pathways. Seventeen acetylated sites in these two pathways were verified by PRM analysis. Our comprehensive analysis revealed key features of GDM/PE-significantly regulated acetylated proteins in the placentas from GDM and PE. The results of signaling pathway analysis focused on ERS and ferroptosis. These findings may help

show abstract

Section: Discussionmentioning

confidence: 76%

Integrated proteome and acetylome analyses unveil protein features of gestational diabetes mellitus and preeclampsia

Tang

et al. 2022

Proteomics

View full text Add to dashboard Cite

show abstract

“…CEBPB (CCAAT enhancer binding protein beta) [38], ACSL4 [39], MBD2 [40], ULK1 [41], NUCB2 [42], TWIST1 [43], HOOK2 [44], CLDN7 [45], TBK1 [46], YIPF6 [47], TFRC (transferrin receptor) [48], ENPP2 [49], SLIT2 [50], MFGE8 [51], FAT1 [52], GPC4 [53], COL6A3 [54], EGFL6 [55], AOC3 [56], CCN2 [57], LYVE1 [58], RARA (retinoic acid receptor alpha) [59], COL18A1 [60], THY1 [61], CD36 [62], PEMT (phosphatidylethanolamine N-methyltransferase) [63], AIF1L [64], OXTR (oxytocin receptor) [65], LMNA (lamin A/C) [66], CXCL14 [67], DKK3 [68], ANGPTL2 [69] and CMTM7 [70] were reported to be associated with obesity, but these genes might be linked with progression of GDM. AHR (aryl hydrocarbon receptor) [71], STS (steroid sulfatase) [72], PLAC1 [73], CYP11A1 [74], PSG11 [75], STAT5B [76], TLR3 [77], FOLR1 [78], HSPB1 [79], HSP90AA1 [80], ANXA4 [81], ATF3 [82], DAPK1 [83], ENTPD1 [84], ABL1 [85], VSIG4 [86], CD99 [87], VWF (von Willebrand factor) [88], PODXL (podocalyxin like) [89], PDPN (podoplanin) [90], RND3 [91], VCAN (versican) [92], AXL (AXL receptor tyrosine kinase) [93], PIEZO1 [94], GAS6 [93], LAMA4 [95], CAV1 [96], DLL1 [97], CD44 [98], CD81 [99], SMAD3 [100], NES (nestin) [101], DCN (decorin) [102], AGTR1 [103], SLIT3 [104], B2M [105], STAT3 [106], STC1 [107] and ADAMTS1 [108] were shown to participate in facilitating the preeclampsia. Majchrzak-Celiń ka et al [109] ...…”

Section: Discussionmentioning

confidence: 99%

Integrated bioinformatics analysis reveals novel key biomarkers and potential candidate small molecule drugs in gestational diabetes mellitus

Vastrad¹,

Vastrad²,

Tengli

2021

Preprint

View full text Add to dashboard Cite

Gestational diabetes mellitus (GDM) is one of the metabolic diseases during pregnancy. The identification of the central molecular mechanisms liable for the disease pathogenesis might lead to the advancement of new therapeutic options. The current investigation aimed to identify central differentially expressed genes (DEGs) in GDM. The transcription profiling by array data (E-MTAB-6418) was obtained from the ArrayExpress database. The DEGs between GDM samples and non GDM samples were analyzed with limma package. Gene ontology (GO) and REACTOME enrichment analysis were performed using ToppGene. Then we constructed the protein-protein interaction (PPI) network of DEGs by the Search Tool for the Retrieval of Interacting Genes database (STRING) and module analysis was performed. Subsequently, we constructed the miRNA-hub gene network and TF-hub gene regulatory network by the miRNet database and NetworkAnalyst database. The validation of hub genes was performed through receiver operating characteristic curve (ROC). Finally, the candidate small molecules as potential drugs to treat GDM were predicted by using molecular docking. Through transcription profiling by array data, a total of 869 DEGs were detected including 439 up regulated and 430 down regulated genes. Biological process analysis of GO enrichment analysis showed these DEGs were mainly enriched in reproduction, nuclear outer membrane-endoplasmic reticulum membrane network, identical protein binding, cell adhesion, supramolecular complex and signaling receptor binding. Signaling pathway enrichment analysis indicated that these DEGs played a vital in cell surface interactions at the vascular wall and extracellular matrix organization. Ten genes, HSP90AA1, EGFR, RPS13, RBX1, PAK1, FYN, ABL1, SMAD3, STAT3, and PRKCA in the center of the PPI network, modules, miRNA-hub gene regulatory network and TF-hub gene regulatory network were associated with GDM, according to ROC analysis. Finally, the most significant small molecules were predicted based on molecular docking. Our results indicated that HSP90AA1, EGFR, RPS13, RBX1, PAK1, FYN, ABL1, SMAD3, STAT3, and PRKCA could be the potential novel biomarkers for GDM diagnosis, prognosis and the promising therapeutic targets. The current might be essential to understanding the molecular mechanism of GDM initiation and development.

show abstract

“…Previous research has examined stress during pregnancy and methylation of glucocorticoid pathway and stress genes, though most of these studies have conducted DNAm analyses in the immediate postpartum period [16][17][18][19][20][21]. In a sample of pregnant women (N = 83) from Belgium, psychosocial stress and cortisol was measured at each trimester, and pregnancy-related anxiety was found to be associated with NR3C1 methylation in cord blood [16].…”

Section: Introductionmentioning

confidence: 99%

“…In a sample of pregnant women (N = 83) from Belgium, psychosocial stress and cortisol was measured at each trimester, and pregnancy-related anxiety was found to be associated with NR3C1 methylation in cord blood [16]. A case-control study of postpartum Mexican women (N = 40) compared women with preeclampsia and normotensive women and found differential methylation patterns in promotor regions of genes, including NR3C1 among women with preeclampsia, suggesting a regulatory role in response to stress in pregnancy [18]. Another study examined chronic and war-related stress among pregnant women (n = 24) from the Democratic Republic of Congo and methylation of HPA genes at birth.…”

Section: Introductionmentioning

confidence: 99%

Stress and DNA Methylation of Blood Leukocytes among Pregnant Latina Women

Barcelona,

Abuaish,

Lee

et al. 2023

Epigenomes

View full text Add to dashboard Cite

Latinas experience physical and psychological stressors in pregnancy leading to increased morbidity and higher risk for adverse birth outcomes. Epigenetic changes, including DNA methylation (DNAm), have been proposed as markers to create more refined risk stratification, yet few of these studies have examined these changes in Latinas. We conducted a secondary analysis of stored blood leukocytes of Latina women (n = 58) enrolled in a larger National Institutes of Health funded R01 project (2011–2016). We examined DNAm on eight candidate stress genes to compare physically and psychologically stressed participants to healthy (low stress) participants. We found unique CpGs that were differentially methylated in stressed women early- and mid-pregnancy compared to the healthy group, though none remained significant after FDR correction. Both physical and psychological stress were associated with hypomethylation at two consecutive CpG sites on NR3C1 in early pregnancy and one CpG site on NR3C1 in mid-pregnancy before adjustment. Stress was also associated with hypomethylation at two CpG sites on FKBP5 in early and mid-pregnancy but were no longer significant after FDR adjustment. Though we did not find statistically significant differences in DNAm during pregnancy between stressed and healthy women in this sample, signals were consistent with previous findings. Future work in larger samples should further examine the associations between stress and DNAm in pregnancy as this mechanism may explain underlying perinatal health inequities.

show abstract

Differential Methylation in Promoter Regions of the Genes NR3C1 and HSP90AA1, Involved in the Regulation, and Bioavailability of Cortisol in Leukocytes of Women With Preeclampsia

Cited by 8 publications

References 22 publications

Integrated proteome and acetylome analyses unveil protein features of gestational diabetes mellitus and preeclampsia

Integrated proteome and acetylome analyses unveil protein features of gestational diabetes mellitus and preeclampsia

Integrated bioinformatics analysis reveals novel key biomarkers and potential candidate small molecule drugs in gestational diabetes mellitus

Stress and DNA Methylation of Blood Leukocytes among Pregnant Latina Women

Contact Info

Product

Resources

About