Placenta Growth Factor Induces Invasion and Activates p70 during Rapamycin Treatment in Trophoblast Cells

Knuth, Allison; Liu, Lawrence; Nielsen, Halden; Merril, Daniel; Torry, Donald S.; Arroyo, Juan A.

doi:10.1111/aji.12327

Cited by 31 publications

(35 citation statements)

References 36 publications

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“…It has been shown that inhibiting the phosphorylation of mTOR down-regulated the PlGF mRNA level (PlGF, a member of the VEGF family proteins) [41]. In agreement with previous study, the relative mRNA level of VEGF-A in placenta was increased by COS supplementing.…”

Section: Discussionsupporting

confidence: 89%

Chitosan oligosaccharide affects antioxidant defense capacity and placental amino acids transport of sows

Xie

Long

et al. 2016

BMC Vet Res

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BackgroundChitosan oligosaccharide (COS) is widely consumed as a functional food due to its multiple health effects, but few studies about COS supplement on placental antioxidant and nutrition transport capacity were reported. Taken pregnant sow as a model, we aimed to investigate the effects of dietary COS supplementation during late gestation on placental amino acids transport and antioxidant defense capacity of sows. From day (d) 85 of gestation to parturition, sixteen pregnant sows were divided into a control group (basal diet without COS supplementation) and a COS group (30 mg COS/kg basal diet). Plasma sample of sow was collected on d 110 of gestation, and placenta tissue was obtained during parturition. Then plasma antioxidant enzyme’s activities, the relative level of oxidant stress related genes, amino acids transport related genes and mTOR pathway molecules in placenta were determined.ResultsResults showed that maternal dietary supplementation with COS increased (P < 0.05) plasma total SOD, caused a downtrend in plasma MDA (0.05 < P < 0.10) on d 110 of gestation. Interestingly, the mRNA expression of some antioxidant genes in the placenta were increased (P < 0.05) and pro-inflammatory cytokines were reduced (P < 0.05) by COS supplement, whereas no significant difference was observed in the activities of placental total SOD and CAT between two groups. Additionally, further study demonstrated that COS feeding stimulated mTOR signaling pathway, increased amino acids transporters expression in placenta.ConclusionsThese observations suggested that COS supplement in sow’s diet during late gestation enhanced antioxidant defense capacity of sows, promoted placental amino acids transport, which may contribute to the health of sows and development of fetus during gestation.

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Section: Discussionsupporting

confidence: 89%

Chitosan oligosaccharide affects antioxidant defense capacity and placental amino acids transport of sows

Xie

Long

et al. 2016

BMC Vet Res

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“…In addition, PIGF is a secreted proangiogenic protein that belongs to the VEGF family. PIGF participates in the development of the intrauterine vascular network, trophoblast invasion, and inflammatory processes [ 43 ]. Decreased maternal serum levels of PIGF during early gestation correlate with an increasing risk of abnormal pregnancy and, specifically, early-onset preeclampsia [ 44 ].…”

Section: Discussionmentioning

confidence: 99%

Effects of Human Umbilical Cord Mesenchymal Stem Cells on Human Trophoblast Cell Functions In Vitro

Huang

Chang

et al. 2016

Stem Cells International

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Trophoblast cell dysfunction is involved in many disorders during pregnancy such as preeclampsia and intrauterine growth restriction. Few treatments exist, however, that target improving trophoblast cell function. Human umbilical cord mesenchymal stem cells (hUCMSCs) are capable of self-renewing, can undergo multilineage differentiation, and have homing abilities; in addition, they have immunomodulatory effects and paracrine properties and thus are a prospective source for cell therapy. To identify whether hUCMSCs can regulate trophoblast cell functions, we treated trophoblast cells with hUCMSC supernatant or cocultured them with hUCMSCs. Both treatments remarkably enhanced the migration and invasion abilities of trophoblast cells and upregulated their proliferation ability. At a certain concentration, hUCMSCs also modulated hCG, PIGF, and sEndoglin levels in the trophoblast culture medium. Thus, hUCMSCs have a positive effect on trophoblast cellular functions, which may provide a new avenue for treatment of placenta-related diseases during pregnancy.

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“…The importance of the JZ is underscored by the previous observation that decreased trophoblast invasion is observed when mTOR activation is inhibited (Knuth et al. ). We therefore conclude that IUGR is correlated with increased 4EBP1 activity in the invading trophoblast cells of the uterine mesometrial compartment, decreased activation of the mTOR protein, and decreased trophoblast invasion in the placenta during maternal hypoxia‐induced IUGR.…”

Section: Discussionmentioning

confidence: 99%

“…Such differential responses suggest alternative mechanisms for these proteins in the placenta during IUGR that has not yet been adequately defined. Our laboratory has shown a direct correlation between mTOR protein activation and trophoblast invasion, suggesting a central role for this pathway in the regulation of trophoblast invasion during IUGR (Knuth et al 2014). We hypothesized that maternal hypoxia will induce IUGR by regulating proteins associated with the mTOR pathway.…”

Section: Introductionmentioning

confidence: 99%

Hypoxia reduces placental mTOR activation in a hypoxia-induced model of intrauterine growth restriction (IUGR)

et al. 2015

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Mammalian target of rapamycin (mTOR) is a protein that regulates cell growth in response to altered nutrient and growth factor availability. Our objective was to assess activated mTOR and its intracellular intermediates p70, and 4EBP1 in placental and invasive trophoblast cells in a hypoxia‐induced model of intrauterine growth restriction (IUGR) in rats. Rats were treated with hypoxia (9%) for 4 days. Placental and fetal weights, as well as conceptus numbers were recorded at the time of necropsy. Immunohistochemistry was used to determine the level of trophoblast invasion and apoptosis. Western blots were used to determine the activation of mTOR, p70, and 4EBP1 in the placenta and the uterine mesometrial compartment. We observed (1) decreased placental (21%) and fetal (24%) weights (P < 0.05); (2) decreased trophoblast invasion; (3) significantly increased active 4EBP1 (28%; P < 0.05) in invasive trophoblast cells yet no changes in the activation of mTOR and p70 proteins; and (4) a significant decrease in the activation of mTOR (48%; P < 0.05) with no differences in p70 or 4EBP1 activation in the placenta. We conclude that the development of IUGR is correlated with decreased activation of the mTOR protein in the placenta and increased 4EBP1 activity in the invading trophoblast. These results provide important insight into the physiological relevance of these pathways. Furthermore, modification of these and other related targets during gestation may alleviate IUGR severity.

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Placenta Growth Factor Induces Invasion and Activates p70 during Rapamycin Treatment in Trophoblast Cells

Abstract: We conclude that first trimester trophoblast invasion is functionally decreased when phosphorylation of mTOR is prevented and this decrease is recovered with the addition of PlGF. Mechanistically, this recovery involves the phosphorylation of p70 independent of mTOR.

Cited by 31 publications

References 36 publications

Chitosan oligosaccharide affects antioxidant defense capacity and placental amino acids transport of sows

Chitosan oligosaccharide affects antioxidant defense capacity and placental amino acids transport of sows

Effects of Human Umbilical Cord Mesenchymal Stem Cells on Human Trophoblast Cell Functions In Vitro

Hypoxia reduces placental mTOR activation in a hypoxia-induced model of intrauterine growth restriction (IUGR)

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