Glucocorticoid exposure altered angiogenic factor expression via Akt/mTOR pathway in rat placenta

Ozmen, Asli; Unek, Gozde; Kipmen-Korgun, Dijle; Cetinkaya, Busra; Avcil, Zeynep; Korgun, Emin Türkay

doi:10.1016/j.aanat.2014.10.007

Cited by 22 publications

(13 citation statements)

References 47 publications

(55 reference statements)

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“…Our data show that mTORC1 inhibition decreases the expression of VEGF in PHT cells, which is in agreement with previous reports showing that rapamycin inhibits VEGF production and signaling in mice adenocarcinoma (Guba et al, 2002). These observations are consistent with the finding that IUGR induced by maternal dexamethasone treatment in the rat is associated with mTORC1 inhibition and decreased expression of angiogenic factors in the placenta (Ozmen et al, 2015). Furthermore, mTORC1 inhibition in PHT cells decreased the expression of CRELD1, a member of a subfamily of epidermal growth factor-related proteins.…”

Section: Discussionsupporting

confidence: 93%

mTORC1 Transcriptional Regulation of Ribosome Subunits, Protein Synthesis, and Molecular Transport in Primary Human Trophoblast Cells

Rosario

Powell

Gupta

et al. 2020

Front. Cell Dev. Biol.

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Mechanistic Target of Rapamycin Complex 1 (mTORC1) serves as positive regulator of placental nutrient transport and mitochondrial respiration. The role of mTORC1 signaling in modulating other placental functions is largely unexplored. We used gene array following silencing of raptor to identify genes regulated by mTORC1 in primary human trophoblast (PHT) cells. Seven hundred and thirty-nine genes were differentially expressed; 487 genes were down-regulated and 252 up-regulated. Bioinformatic analyses demonstrated that inhibition of mTORC1 resulted in decreased expression of genes encoding ribosomal proteins in the 60S and 40S ribosome subunits. Furthermore, down-regulated genes were functionally enriched in genes involved in eIF2, sirtuin and mTOR signaling, mitochondrial function, and glutamine and zinc transport. Stress response genes were enriched among up-regulated genes following mTORC1 inhibition. The protein expression of ribosomal proteins RPL26 (RPL26) and Ribosomal Protein S10 (RPS10) was decreased and positively correlated to mTORC1 signaling and System A amino acid transport in human placentas collected from pregnancies complicated by intrauterine growth restriction (IUGR). In conclusion, mTORC1 signaling regulates the expression of trophoblast genes involved in ribosome and protein synthesis, mitochondrial function, lipid metabolism, nutrient transport, and angiogenesis, representing novel links between mTOR signaling and multiple placental functions critical for normal fetal growth and development.

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Section: Discussionsupporting

confidence: 93%

mTORC1 Transcriptional Regulation of Ribosome Subunits, Protein Synthesis, and Molecular Transport in Primary Human Trophoblast Cells

Rosario

Powell

Gupta

et al. 2020

Front. Cell Dev. Biol.

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“…3c , the top 10 enriched pathways were focal adhesion, ECM-receptor interaction, regulation of actin cytoskeleton, metabolic pathways, DNA replication, phosphatidylinositol signaling system, Epstein-Barr virus infection, propanoate metabolism, cell cycle, and the mammalian target of rapamycin (mTOR) signaling pathway. These results indicated that host genes of differentially expressed circRNAs in PE were involved in the mTOR signaling pathway that is related to angiogenic factor expression in the placenta of rats [ 23 ].…”

Section: Resultsmentioning

confidence: 99%

Competing endogenous RNA expression profiling in pre-eclampsia identifies hsa_circ_0036877 as a potential novel blood biomarker for early pre-eclampsia

et al. 2018

Clin Epigenet

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BackgroundThe etiology and pathogenesis of pre-eclampsia (PE) is unclear, and there is no ideal early clinical biomarker for prediction of PE. The competing endogenous RNA (ceRNA) hypothesis is a new approach to uncover the molecular pathology of PE. The first aim of this study was to perform messenger RNA, long non-coding RNA, and circular RNA (circRNA) expression profiling of human normal and severe pre-eclampsia (SPE) placentas. circRNA, which has a stable structure, is a more suitable biomarker than other types of RNA. Therefore, the second aim of our study was to select some differentially expressed circRNAs in PE placentas as early clinical biomarkers of PE in blood circulation.ResultsUsing microarray analysis, we investigated differentially expressed ceRNAs in human normal and SPE placentas. Bioinformatics, such as gene ontology, KEGG pathway, and ceRNA network analyses, were performed to evaluate the microarray data and gain further insights into the biological processes. RNAs (Chd5, Furin, lnc-ELAVL4-9:1, lnc-RAP1GAP2-5:2, hsa_circ_0036877, hsa_circ_0036878, hsa_circ_0055724, hsa_circ_0049730, and hsa_circ_0036474) were validated by quantitative real-time PCR (qRT-PCR). RNA immunoprecipitation (RIP) of AGO2 in htra-8 cells and qRT-PCR analysis of hsa_circ_0036877 expression in maternal whole peripheral blood samples of participants were then conducted to confirm that hsa_circ_0036877 is a ceRNA and potential novel blood biomarker for early PE, respectively.ConclusionOur study is the first systematic profiling of ceRNAs in placentas of PE patients and revealed the global ceRNA network integration in PE. Moreover, hsa_circ_0036877 can function as a ceRNA and serve as a potential novel blood biomarker for early PE.Electronic supplementary materialThe online version of this article (10.1186/s13148-018-0482-3) contains supplementary material, which is available to authorized users.

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“…In animal models of maternal prenatal stress, increased glucocorticoid levels are correlated with intrauterine growth restriction. Fetal growth restriction mediated through excess endogenous corticosterone or synthetic dexamethasone exposure results in altered placental transporter function and glucose transport and reduced expression of pro-angiogenic factors [27, 28]. Glucocorticoid exposure at the maternal-fetal interface is in part regulated through the expression of the 11β-HSD isoenzymes in discrete maternal and fetal compartments [29].…”

Section: Glucocorticoids Regulate the Function Of Organs In The Repromentioning

confidence: 99%

Glucocorticoids and Reproduction: Traffic Control on the Road to Reproduction

Whirledge

Cidlowski

2017

Trends in Endocrinology & Metabolism

135

103

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Glucocorticoids are steroid hormones that regulate diverse cellular functions and are essential to facilitate normal physiology. Yet, stress-induced levels of glucocorticoids result in several pathologies including profound reproductive dysfunction. Compelling new evidence indicates glucocorticoids are crucial to the establishment and maintenance of reproductive function. The fertility promoting or inhibiting activity of glucocorticoids depends on timing, dose, and glucocorticoid-responsiveness within a given tissue, which is mediated by the glucocorticoid receptor. The glucocorticoid receptor gene and protein are subject to cellular processing, contributing to signaling diversity and providing a mechanism by which both physiological and stress-induced levels of glucocorticoids function in a cell-specific function. Understanding how glucocorticoids regulate fertility and infertility may lead to novel approaches to the regulation of reproductive function.

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Glucocorticoid exposure altered angiogenic factor expression via Akt/mTOR pathway in rat placenta

Cited by 22 publications

References 47 publications

mTORC1 Transcriptional Regulation of Ribosome Subunits, Protein Synthesis, and Molecular Transport in Primary Human Trophoblast Cells

mTORC1 Transcriptional Regulation of Ribosome Subunits, Protein Synthesis, and Molecular Transport in Primary Human Trophoblast Cells

Competing endogenous RNA expression profiling in pre-eclampsia identifies hsa_circ_0036877 as a potential novel blood biomarker for early pre-eclampsia

Glucocorticoids and Reproduction: Traffic Control on the Road to Reproduction

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