The NR4A receptors Nurr1 and Nur77 are increased in human placenta from women with gestational diabetes

Lappas, Martha

doi:10.1016/j.placenta.2014.08.089

Cited by 13 publications

(17 citation statements)

References 68 publications

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“…There is extensive evidence that show human placenta and adipose tissue are important sites involved in the propagation of this maternal inflammation [15, 21, 22, 30, 32, 40–48]. In this study, human placenta and adipose tissue (omental and subcutaneous) were stimulated with the pro-inflammatory cytokines TNF-α and IL-1β in order to induce an inflammatory state.…”

Section: Discussionmentioning

confidence: 99%

“…The samples were then blotted dry on filter paper; 100 mg wet weight (for placenta and adipose) or 50 mg wet weight (for skeletal muscle) per well was transferred to a 24-well tissue culture plate and incubated in 1 ml DMEM for 20 h. To determine the effects of resveratrol on placental, omental and subcutaneous adipose tissue and skeletal muscle, these tissues were incubated in 10 μg/ml LPS, 50 μg/ml poly(I:C), 10 ng/ml TNF-α, 5 ng/ml IL-1β with or without 200 μM resveratrol (AdooQ BioScience, Irvine, CA, USA). The optimised concentration of resveratrol [24] and the inflammatory mediators [20, 24, 30] were determined by previously published studies. After final incubation, tissue and media were collected separately and stored at -80°C for further analysis as detailed below.…”

Section: Methodsmentioning

confidence: 99%

“…Total RNA was extracted from tissues using TRIsure reagent according to manufacturer’s instructions (Bioline, Alexandria, NSW, Australia), as previously described [30]. RNA concentration and purity were determined using a NanoDrop ND1000 spectrophotometer (Thermo Scientific, Pittsburgh, PA).…”

Section: Methodsmentioning

confidence: 99%

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Resveratrol ameliorates the chemical and microbial induction of inflammation and insulin resistance in human placenta, adipose tissue and skeletal muscle

et al. 2017

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Gestational diabetes mellitus (GDM), which complicates up to 20% of all pregnancies, is associated with low-grade maternal inflammation and peripheral insulin resistance. Sterile inflammation and infection are key mediators of this inflammation and peripheral insulin resistance. Resveratrol, a stilbene-type phytophenol, has been implicated to exert beneficial properties including potent anti-inflammatory and antidiabetic effects in non-pregnant humans and experimental animal models of GDM. However, studies showing the effects of resveratrol on inflammation and insulin resistance associated with GDM in human tissues have been limited. In this study, human placenta, adipose (omental and subcutaneous) tissue and skeletal muscle were stimulated with pro-inflammatory cytokines TNF-α and IL-1β, the bacterial product lipopolysaccharide (LPS) and the synthetic viral dsRNA analogue polyinosinic:polycytidylic acid (poly(I:C)) to induce a GDM-like model. Treatment with resveratrol significantly reduced the expression and secretion of pro-inflammatory cytokines IL-6, IL-1α, IL-1β and pro-inflammatory chemokines IL-8 and MCP-1 in human placenta and omental and subcutaneous adipose tissue. Resveratrol also significantly restored the defects in the insulin signalling pathway and glucose uptake induced by TNF-α, LPS and poly(I:C). Collectively, these findings suggest that resveratrol reduces inflammation and insulin resistance induced by chemical and microbial products. Resveratrol may be a useful preventative therapeutic for pregnancies complicated by inflammation and insulin resistance, like GDM.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Resveratrol ameliorates the chemical and microbial induction of inflammation and insulin resistance in human placenta, adipose tissue and skeletal muscle

et al. 2017

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“…Isolation and purification of primary villous trophoblast cells was performed using fresh placenta obtained from normal healthy pregnant women at term caesarean section. Placental villous cytotrophoblasts were isolated as previously described (Lappas 2014) by DNase/trypsin digestion and purified by separation on a Percoll gradient. Briefly, placental villous tissue (~25 g) was dissected and washed in saline and then digested three times in a HEPES-buffered salt solution containing 0.25% trypsin and 0.2 mg/mL DNAse.…”

Section: Isolation Of Primary Villous Trophoblast Cells and Umbilicalmentioning

confidence: 99%

“…To determine the expression of BRD4 in placenta, immunohistochemistry (IHC) was performed on paraffin sections as described previously using the IHC Select HRP Detection Set (Merck Millipore) (Lappas 2014). Briefly, sections were deparaffinised followed by an antigen retrieval step (boiled in 10 mM Tris, 1 mM EDTA, pH 9.0 for 10 min followed by 20-min incubation) and then endogenous peroxidases were inactivated by adding 3% hydrogen peroxide for 10 min.…”

Section: Immunohistochemistrymentioning

confidence: 99%

Bromodomain protein BRD4 is increased in human placentas from women with early-onset preeclampsia

Liong¹,

Barker²,

Lappas³

2018

Reproduction

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Preeclampsia affects 5% of all pregnancies and is a serious disorder of pregnancy, characterised by high maternal blood pressure, placental hypoxia, fluid retention (oedema) and proteinuria. Women with preeclampsia are associated with exaggerated levels of pro-inflammatory cytokines, chemokines and anti-angiogenic factors such as soluble fms-like tyrosine kinase-1 (sFLT1). Studies in non-gestational tissues have described the bromodomain (BRD) and extraterminal family of proteins, in particular BRD4 to play a critical role in propagating inflammation and is currently a therapeutic target for treating cancer, lung inflammation and asthma. The aims of this study were to: (i) determine the effect of severe early-onset preeclampsia on placental BRD4 expression; (ii) the effect of loss of BRD4 function by siRNA-targeted knockdown or with the BRD inhibitor JQ1 in human primary trophoblast cells and human umbilical vein endothelial cells (HUVECs) on TNF-stimulated production of pro-inflammatory mediators, cell adhesion molecules and anti-angiogenic markers and (iii) the effect of BRD4 suppression on placental sFLT1 secretion under hypoxia conditions and in preeclampic placenta. BRD4 mRNA expression was significantly increased (sevenfold) in severe early-onset preeclampsia placenta. BRD4 silencing resulted in a significant reduction in TNF-induced ,, , and - mRNA expression and IL6, CXCL8, CCL2, CXCL1 and sFLT1 secretion in primary trophoblast and HUVECs. Additionally, JQ1 treatment significantly reduced placental sFLT1 secretion under hypoxic conditions and in preterm preeclamptic placenta. In conclusion, these findings suggest BRD4 may play a central role in propagating inflammation and endothelial dysfunction associated with the pathophysiology of early-onset preeclampsia.

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Orphan nuclear receptor NUR77 relieves insulin resistance in HTR-8/SVneo trophoblast cells through activation of autophagy and insulin signaling

Bai

et al. 2022

J Physiol Biochem

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The NR4A receptors Nurr1 and Nur77 are increased in human placenta from women with gestational diabetes

Cited by 13 publications

References 68 publications

Resveratrol ameliorates the chemical and microbial induction of inflammation and insulin resistance in human placenta, adipose tissue and skeletal muscle

Resveratrol ameliorates the chemical and microbial induction of inflammation and insulin resistance in human placenta, adipose tissue and skeletal muscle

Bromodomain protein BRD4 is increased in human placentas from women with early-onset preeclampsia

Orphan nuclear receptor NUR77 relieves insulin resistance in HTR-8/SVneo trophoblast cells through activation of autophagy and insulin signaling

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