MicroRNAome in decidua: a new approach to assess the maintenance of pregnancy

Wang, Yu; Lv, Yang; Wu, Liyan; Gong, Chunling; Sun, Jiajia; Chen, Xiujuan; Chen, Yan; Yang, Lei; Zhang, Yan; Yang, Xukui; Bai, Chunling; Wei, Zhuying; Li, Guangpeng

doi:10.1016/j.fertnstert.2015.01.003

Cited by 27 publications

(25 citation statements)

References 32 publications

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“…SGK1 activity and expression are both suppressed in the midsecretory endometrial stromal cells of women suffering from RPL, which sensitizes these cells to oxidative cell death 20. This down-regulation of SGK1 has been reported to inversely correlate with miR-199b-5p up-regulation in the decidua of patients with early spontaneous miscarriage, and this correlation was validated in the CBA/J × DBA/2 mouse model of miscarriage 21. Nevertheless, the mechanistic underpinnings of SGK1 down-regulation associated with pregnancy loss are not completely understood.…”

Section: Introductionmentioning

confidence: 78%

Estradiol Suppresses TLR4-triggered Apoptosis of Decidual Stromal Cells and Drives an Anti-inflammatory T_H2 Shift by Activating SGK1

Lou¹,

Hu²,

Wang³

et al. 2017

Int. J. Biol. Sci.

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A pro-inflammatory cytokine profile at the feto-maternal interface may predispose immune maladaptation notably in early miscarriages. We investigated the involvement of estradiol (E2)-activated serum-glucocorticoid regulated kinase 1 (SGK1) in preserving the tolerogenic and pro-survival intrauterine microenvironment beneficial to gestation maintenance. Decidual SGK1 was down-regulated in early miscarriage, consistent with the lower serum E2 concentration seen in pregnancy loss. Lipopolysaccharide (LPS)/Toll-like receptors 4 (TLR4) signaling induced apoptosis and the pro-inflammatory T helper type (TH) 1 response of decidual stromal cells (DSCs) were associated with miscarriage. SGK1 activation was suppressed by LPS/TLR4 signaling and would be rescued by E2 administration via the PI3K signaling pathway in DSCs. SGK1 activation attenuated TLR4-mediated cell apoptosis, while promoting cell viability of DSCs by up-regulating the pro-survival genes BCL2 and XIAP, and enhancing the phosphorylation of FOXO1. Furthermore, E2-induced SGK1 activation reduced the secretion of pro-inflammatory TH1 cytokines, and promoted the generation of TH2 cytokines and elevated IRF4 mRNA and protein levels in LPS-incubated DSCs. Pharmacologic inhibition of SGK1 or suppression by small interfering (si) RNA increased the phosphorylation and nuclear translocation of NF-κB to reverse the pro-TH2 and anti-inflammatory effects of E2 pretreatment, leading to compromised pregnancy. These findings suggest that the E2-mediated SGK1 activation suppressed LPS-mediated apoptosis and promoted the anti-inflammatory TH2 responses in DSCs, ultimately contributing to a successful pregnancy.

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Section: Introductionmentioning

confidence: 78%

Estradiol Suppresses TLR4-triggered Apoptosis of Decidual Stromal Cells and Drives an Anti-inflammatory T_H2 Shift by Activating SGK1

Lou¹,

Hu²,

Wang³

et al. 2017

Int. J. Biol. Sci.

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“…Consistently, Wang et al . have reported low levels of SGK1 expression in patients with miscarriages and its inverse correlation with miR‐199b‐5p. This suggests that there are likely to be other miRNAs that are involved in the down‐regulation of SGK1.…”

Section: Discussionmentioning

confidence: 99%

Novel mechanism of miRNA‐365‐regulated trophoblast apoptosis in recurrent miscarriage

Zhao

Shen

Cao³

et al. 2017

J Cellular Molecular Medi

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Clinical pregnancies increasingly end in recurrent miscarriage (RM) during the first trimester, with genetic factors shouldering the main responsibility. MicroRNAs (miRNAs) regulate gene expression in a wide array of important biological processes. We examined the potential role of dysregulated miRNAs in RM pathogenesis and trophoblast development as an approach to elucidate the molecular mechanism behind RM. miRNA profiles from clinical specimens of RM and induced abortion (IA) were compared, and several miRNAs were found to be aberrantly expressed in RM samples. Among the miRNAs, miR‐365 was significantly differentially expressed in RM decidual tissues. Furthermore, our results demonstrate that miR‐365 functions as an upstream regulator of MDM2/p53 expression, cell cycle progression and apoptosis in trophoblasts. Bioinformatic prediction and experimental validation assays identified SGK1 as a direct target of miR‐365; consistently, its protein levels were low in decidual tissues. Additionally, functional studies revealed that SGK1 silencing elicits cell cycle arrest and apoptosis in trophoblasts and that SGK1 overexpression attenuates the effects of miR‐365 on apoptosis and MDM2/p53 expression. Collectively, our data provide evidence that the up‐regulation of miR‐365 may contribute to RM by decreasing SGK1 expression, which suggests its potential utility as a prognostic biomarker and therapeutic target for RM.

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“…Expression of SGK-1 has also been confirmed at both the molecular and protein level in decidua with decreased SGK-1 expression being associated with miscarriage [53].…”

Section: The Placenta As a Salt-sensing Organmentioning

confidence: 90%

Salt, aldosterone and extrarenal Na+ - sensitive responses in pregnancy

Scaife

Mohaupt

2017

Placenta

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Outside of pregnancy excessive salt consumption is known to be harmful being linked to increased blood pressure and cardiovascular disease. However, pregnancy represents a major change to a woman's physiology resulting in an intimate adaptation to environmental conditions. It is now becoming apparent that salt is essential for a number of these changes during pregnancy including haematological, cardiac adaptations as well as directly influencing placental development and the uteroplacental immune environment. The present review discusses the important role that salt has during normal pregnancy and evidence will also be presented to show how the placenta may act as a salt sensing organ temporarily, yet substantially regulating maternal blood pressure.

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MicroRNAome in decidua: a new approach to assess the maintenance of pregnancy

Cited by 27 publications

References 32 publications

Estradiol Suppresses TLR4-triggered Apoptosis of Decidual Stromal Cells and Drives an Anti-inflammatory T_H2 Shift by Activating SGK1

Estradiol Suppresses TLR4-triggered Apoptosis of Decidual Stromal Cells and Drives an Anti-inflammatory T_H2 Shift by Activating SGK1

Novel mechanism of miRNA‐365‐regulated trophoblast apoptosis in recurrent miscarriage

Salt, aldosterone and extrarenal Na+ - sensitive responses in pregnancy

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MicroRNAome in decidua: a new approach to assess the maintenance of pregnancy

Cited by 27 publications

References 32 publications

Estradiol Suppresses TLR4-triggered Apoptosis of Decidual Stromal Cells and Drives an Anti-inflammatory TH2 Shift by Activating SGK1

Estradiol Suppresses TLR4-triggered Apoptosis of Decidual Stromal Cells and Drives an Anti-inflammatory TH2 Shift by Activating SGK1

Novel mechanism of miRNA‐365‐regulated trophoblast apoptosis in recurrent miscarriage

Salt, aldosterone and extrarenal Na+ - sensitive responses in pregnancy

Contact Info

Product

Resources

About

Estradiol Suppresses TLR4-triggered Apoptosis of Decidual Stromal Cells and Drives an Anti-inflammatory T_H2 Shift by Activating SGK1

Estradiol Suppresses TLR4-triggered Apoptosis of Decidual Stromal Cells and Drives an Anti-inflammatory T_H2 Shift by Activating SGK1