Maternal whole blood cell miRNA-340 is elevated in gestational diabetes and inversely regulated by glucose and insulin

Stirm, Laura; Huypens, Peter; Sass, Steffen; Batra, Richa; Fritsche, Louise; Brucker, Sara Y.; Abele, Harald; Hennige, Anita M.; Theis, Fabian J.; Beckers, Johannes; Angelis, Martin Hrabé de; Fritsche, Andreas; Häring, Hans‐Ulrich; Staiger, Harald

doi:10.1038/s41598-018-19200-9

Cited by 45 publications

(56 citation statements)

References 41 publications

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“…Placenta and maternal blood expression profiles of healthy pregnancies (GSE85307 and GSE24129) [ 45,46 ] and pregnancies with complications (GSE85307, GSE92772, GSE24129, and GSE70493) [ 45–48 ] were downloaded from the GEO database. Normalized gene expression values were processed using GEO query in R (ver.…”

Section: Methodsmentioning

confidence: 99%

Whole‐Genome Promoter Profiling of Plasma DNA Exhibits Diagnostic Value for Placenta‐Origin Pregnancy Complications

et al. 2020

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Placenta‐origin pregnancy complications, including preeclampsia (PE), gestational diabetes mellitus (GDM), fetal growth restriction (FGR), and macrosomia (MA) are common occurrences in pregnancy, resulting in significant morbidity and mortality for both mother and fetus. However, despite their frequency, there are no reliable methods for the early diagnosis of these complications. Since cfDNA is mainly derived from placental trophoblasts and maternal hematopoietic cells, it might have information for gene expression which can be used for disease prediction. Here, low coverage whole‐genome sequencing on plasma DNA from 2,199 pregnancies is performed based on retrospective cohorts of 3,200 pregnant women. Read depth in the promoter regions is examined to define read‐depth distribution patterns of promoters for pregnancy complications and controls. Using machine learning methods, classifiers for predicting pregnancy complications are developed. Using these classifiers, complications are successfully predicted with an accuracy of 80.3%, 78.9%, 72.1%, and 83.0% for MA, FGR, GDM, and PE, respectively. The findings suggest that promoter profiling of cfDNA may be used as a biological biomarker for predicting pregnancy complications at early gestational age.

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Section: Methodsmentioning

confidence: 99%

Whole‐Genome Promoter Profiling of Plasma DNA Exhibits Diagnostic Value for Placenta‐Origin Pregnancy Complications

et al. 2020

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“…Functional analyses of these miRNAs provided support for their role in the development of GDM [ 141 , 142 , 143 , 144 ]. Many other miRNAs were reported to exhibit altered expression during GDM, although these were identified in single studies only ( Table 3 ).…”

Section: Micrornasmentioning

confidence: 99%

Molecular Biomarkers for Gestational Diabetes Mellitus

Dias

Pheiffer

Abrahams

et al. 2018

IJMS

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Gestational diabetes mellitus (GDM) is a growing public health problem worldwide. The condition is associated with perinatal complications and an increased risk for future metabolic disease in both mothers and their offspring. In recent years, molecular biomarkers received considerable interest as screening tools for GDM. The purpose of this review is to provide an overview of the current status of single-nucleotide polymorphisms (SNPs), DNA methylation, and microRNAs as biomarkers for GDM. PubMed, Scopus, and Web of Science were searched for articles published between January 1990 and August 2018. The search terms included “gestational diabetes mellitus”, “blood”, “single-nucleotide polymorphism (SNP)”, “DNA methylation”, and “microRNAs”, including corresponding synonyms and associated terms for each word. This review updates current knowledge of the candidacy of these molecular biomarkers for GDM with recommendations for future research avenues.

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“…47 In addition, miR-340 was elevated in the maternal whole blood of patients with gestational diabetes and inversely regulated by insulin and glucose. 48 These data suggest that miR-340 is differentially expressed and has multiple functions in a wide variety of settings. Here, we found that miRNA-340 was down-…”

Section: Discussionmentioning

confidence: 97%

CD226 deficiency on regulatory T cells aggravates renal fibrosis via up-regulation of Th2 cytokines through miR-340

Zhang

Liu

et al. 2019

Journal of Leukocyte Biology

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In this study, we observed that deletion of CD226 on regulatory T cells (Tregs) precedes renal fibrosis in a mouse unilateral ureteral obstruction (UUO) model. First, we generated Treg‐specific CD226 gene knockout mice (CD226fl/fl Foxp3YFP‐Cre). Next, CD226fl/fl Foxp3YFP‐Cre mice and Foxp3YFP‐Cre control mice were subjected to UUO surgery. Pathologic analysis and Sirius red and Masson's trichrome staining showed that the kidneys of CD226fl/fl Foxp3YFP‐Cre mice following UUO showed much more severe interstitial fibrosis than Foxp3YFP‐Cre control mice at days 10 and 20. Additionally, CD226fl/fl Foxp3YFP‐Cre mice showed increased fibronectin expression, as demonstrated by immunohistochemistry (IHC) staining. Although Treg cell‐restricted CD226 deficiency showed increased Foxp3+ expression, expression of the cell surface functional molecule CD103 was significantly reduced, indicating impaired homeostasis in the Tregs of CD226fl/fl Foxp3YFP‐Cre mice. To better understand CD226 function, RNA sequencing (RNA‐Seq) analysis was conducted in Tregs isolated from CD226fl/fl Foxp3YFP‐Cre and Foxp3YFP‐Cre mice. RNA‐Seq data showed that the helper T cell (Th) 2‐related cytokines IL‐4 and IL‐10 were significantly up‐regulated in CD226 deficient Tregs. In addition, mRNA analysis of kidney samples from the mice following UUO by qPCR also showed increased IL‐4 and IL‐10 expression in CD226fl/fl Foxp3YFP‐Cre mice, as well as elevated TGF‐β1 levels, indicating that CD226 deficiency in Tregs resulted in the acquisition of the ability to produce Th2 cytokines. Finally, we found that microRNA‐340 (miR‐340), which was down‐regulated in Tregs isolated from CD226fl/fl Foxp3YFP‐Cre mice, directly regulated IL‐4 gene expression in vitro. These data suggest that the promotion of CD226 signaling on Tregs is a therapeutic target for renal disease.

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Maternal whole blood cell miRNA-340 is elevated in gestational diabetes and inversely regulated by glucose and insulin

Cited by 45 publications

References 41 publications

Whole‐Genome Promoter Profiling of Plasma DNA Exhibits Diagnostic Value for Placenta‐Origin Pregnancy Complications

Whole‐Genome Promoter Profiling of Plasma DNA Exhibits Diagnostic Value for Placenta‐Origin Pregnancy Complications

Molecular Biomarkers for Gestational Diabetes Mellitus

CD226 deficiency on regulatory T cells aggravates renal fibrosis via up-regulation of Th2 cytokines through miR-340

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