Mechanism of neutrophil extracellular traps generation and their role in trophoblasts apoptosis in gestational diabetes mellitus

Shen, Di; Lu, Yuan; Li, Guangzhen; Hu, Min; Li, Shanling; Jiang, Hui; Zhang, Meihua; Wang, Xietong

doi:10.1016/j.cellsig.2021.110168

Cited by 17 publications

(11 citation statements)

References 25 publications

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“…Hyperglycemia can induce trophoblast inflammation and autophagy, inhibit trophoblast migration and invasion (156)(157)(158). Neutrophils in GDM are over-activated and release excessive neutrophil extracellular traps (NETs) (159,160). Excessive NETs hinder the blood circulation in the villous space, resulting in placental ischemia, which is related to the occurrence of PE (161)(162)(163).…”

Section: Mechanism and Predictive Markersmentioning

confidence: 99%

Gestational Diabetes Mellitus and Preeclampsia: Correlation and Influencing Factors

Yang

2022

Front. Cardiovasc. Med.

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Gestational diabetes mellitus (GDM) and preeclampsia (PE) are common pregnancy complications with similar risk factors and pathophysiological changes. Evidence from previous studies suggests that the incidence of PE is significantly increased in women with GDM, but whether GDM is independently related to the occurrence of PE has remained controversial. GDM complicated by PE further increases perinatal adverse events with greater impact on the future maternal and offspring health. Identify factors associated with PE in women with GDM women, specifically those that are controllable, is important for improving pregnancy outcomes. This paper provides the findings of a review on the correlation between GDM and PE, factors associated with PE in women with GDM, possible mechanisms, and predictive markers. Most studies concluded that GDM is independently associated with PE in singleton pregnancy, and optimizing the treatment and management of GDM can reduce the incidence of PE, which is very helpful to improve pregnancy outcomes.

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Section: Mechanism and Predictive Markersmentioning

confidence: 99%

Gestational Diabetes Mellitus and Preeclampsia: Correlation and Influencing Factors

Yang

2022

Front. Cardiovasc. Med.

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“…In high fat dietfed LDL receptor-deficient mice, adiponectin overexpression by adenoviral gene transfer attenuated macrophage burden and the levels of proinflammatory mediators such as tumor necrosis factor-α, interleukin-6, interleukin-12, and C-C motif chemokine ligand 2 whereas increased anti-inflammatory interleukin-10 in the aortas after subcutaneous angiotensin II infusion [48]. Additionally, adiponectin treatment promoted anti-inflammatory alternative macrophage activation but attenuated proinflammatory neutrophil extracellular trap formation [49][50][51][52].…”

Section: Discussionmentioning

confidence: 99%

Adiponectin Protects Hypoxia/Reoxygenation-Induced Cardiomyocyte Injury by Suppressing Autophagy

Guo

Zhu

Liu

2022

Journal of Immunology Research

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Adiponectin is a cytokine produced by adipocytes and acts as a potential cardioprotective agent and plays an important role in myocardial ischemia/reperfusion injury. In a myocardial hypoxia/reoxygenation model using neonatal rat ventricular myocytes, we investigated the contribution of adiponectin-mediated autophagy to its cardioprotective effects. Cardiomyocytes were exposed to hypoxia/reoxygenation pretreated with or without adiponectin in the presence of absence of rapamycin. Cell viability was analyzed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide method. Western blotting assay was used to determine the expression levels of microtubule-associated proteins 1A/1B light chain 3B (LC3B), adenosine monophosphate-activated protein kinase (AMPK), mammalian target of rapamycin (mTOR), p62/sequestosome 1, unc-51 like autophagy activating kinase 1 (ULK1), and Beclin-1. Autophagosome formation was detected by monodansylcadaverine staining. We found that hypoxia induced a time dependent decline in cardiomyocyte viability, and increase in autophagy and reoxygenation further augmented hypoxia-induced autophagy induction and consequently reduced cell viability. Adiponectin treatment alleviated hypoxia/reoxygenation-induced cellular damage and autophagy in cardiomyocytes. Adiponectin treatment also attenuated hypoxia/reoxygenation-promoted cardiomyocyte autophagy even in the presence of another autophagy stimulator rapamycin in part by inhibiting vacuolar hydron-adenosine triphosphatase. Additionally, autophagy suppression by adiponectin during hypoxia/reoxygenation was associated with the attenuated phosphorylation of AMPK and ULK1, augmented phosphorylation of mTOR, and the reduced protein expression levels of Beclin-1 in cardiomyocytes. Taken together, these results suggest that adiponectin protects ischemia/reperfusion-induced cardiomyocytes by suppressing autophagy in part through AMPK/mTOR/ULK1/Beclin-1 signaling pathway.

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“…GO and REACTOME pathway enrichment analyses were used to investigate the interactions of DEGs. Pathways include hemostasis [57], neutrophil degranulation [58], immune system [59] and cytokine signaling in immune system [60] are responsible for progression of GDM. LGR5 [61], GREM1 [62], GLRA3 [63], NEUROD4 [64], CYP2J2 [65], KCNH6 [66], LBP (lipopolysaccharide binding protein) [67], CXCL14 [68], RGN (regucalcin) [69], NPY2R [70], SERPINB13 [71], WNT5A [72], EDA (ectodysplasin A) [73], HSD11B2 [74], ACVR1C [75], NEUROD1 [76], SLIT2 [77], PPARGC1A [78], IGF1 [79], OSR1 [80], CYP46A1 [81], TLR3 [82], BMP7 [83], SELP (selectin P) [84], HLA-A [85], NOTCH2 [86], LRP1 [87], CLU (clusterin) [88], FCN1 [89], CDKN1A [90], SMAD3 [91], HLA-E [92], PTPRC (protein tyrosine phosphatase receptor type C) [93], MYH9 [94], JAK3 [95], IL6R [96], TIMP1 [97], DOCK8 [98], TNFRSF1B [99], ITGAL (integrin subunit alpha L) [100], CD47 [101], RARA (retinoic acid receptor alpha) [102], DGKD (diacylglycerol kinase delta) [103], PLEK (pleckstrin) [104], PREX1 [105], BSCL2 [106], PANX1 [107], IRF7 [108], NOTCH1 [109], STIM1 [110], TRIM13 [111], LRBA (LPS responsive beige-like anchor protein) [112], CXCR4 [113], MDM4 [114], MYO9B [115] and PDE5A [116] were revealed to be expressed in diabetes mellitus, but these genes might be novel targets for GDM.…”

Section: Discussionmentioning

confidence: 99%

Identification of differentially expressed genes and signaling pathways in gestational diabetes mellitus by integrated bioinformatics analysis

Vastrad¹,

Vastrad²

2021

Preprint

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Gestational diabetes mellitus (GDM) is a metabolic disorder during pregnancy. Numerous biomarkers have been identified that are linked with the occurrence and development of GDM. The aim of this investigation was to identify differentially expressed genes (DEGs) in GDM using a bioinformatics approach to elucidate their molecular pathogenesis. GDM associated expression profiling by high throughput sequencing dataset (GSE154377) was obtained from Gene Expression Omnibus (GEO) database including 28 normal pregnancy samples and 33 GDM samples. DEGs were identified using DESeq2. The gene ontology (GO) and REACTOME pathway enrichments of DEGs were performed by g:Profiler. Protein-protein interaction (PPI) networks were assembled with Cytoscape software and separated into modules using the PEWCC1 algorithm. MiRNA-hub gene regulatory network and TF-hub gene regulatory network were performed with the miRNet database and NetworkAnalyst database. Receiver Operating Characteristic (ROC) analyses was conducted to validate the hub genes. A total of 953 DEGs were identified, of which 478 DEGs were up regulated and 475 DEGs were down regulated. Furthermore, GO and REACTOME pathway enrichment analysis demonstrated that these DEGs were mainly enriched in multicellular organismal process, cell activation, formation of the cornified envelope and hemostasis. TRIM54, ELAVL2, PTN, KIT, BMPR1B, APP, SRC, ITGA4, RPA1 and ACTB were identified as key genes in the PPI network, miRNA-hub gene regulatory network and TF-hub gene regulatory network. TRIM54, ELAVL2, PTN, KIT, BMPR1B, APP, SRC, ITGA4, RPA1 and ACTB in GDM were validated using ROC analysis. This investigation provides further insights into the molecular pathogenesis of GDM, which might facilitate the diagnosis and treatment of GDM.

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Mechanism of neutrophil extracellular traps generation and their role in trophoblasts apoptosis in gestational diabetes mellitus

Cited by 17 publications

References 25 publications

Gestational Diabetes Mellitus and Preeclampsia: Correlation and Influencing Factors

Gestational Diabetes Mellitus and Preeclampsia: Correlation and Influencing Factors

Adiponectin Protects Hypoxia/Reoxygenation-Induced Cardiomyocyte Injury by Suppressing Autophagy

Identification of differentially expressed genes and signaling pathways in gestational diabetes mellitus by integrated bioinformatics analysis

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