Mechanistic Target of Rapamycin Complex 2 Regulation of the Primary Human Trophoblast Cell Transcriptome

Mechanistic Target of Rapamycin Complex 2 (mTORC2) regulates placental amino acid and folate transport. However, the role of mTORC2 in modulating other placental functions is largely unexplored. We used a gene array following the silencing of rictor to identify genes regulated by mTORC2 in primary h...

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Autores principales:	Fredrick J. Rosario, Amy Catherine Kelly, Madhulika B. Gupta, Theresa L. Powell, Laura Cox, Thomas Jansson
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	placenta maternal-fetal exchange human nutrient sensor gene array Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/eac172fa88e44145b5c660602dfea016
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spelling	oai:doaj.org-article:eac172fa88e44145b5c660602dfea0162021-11-04T05:25:23ZMechanistic Target of Rapamycin Complex 2 Regulation of the Primary Human Trophoblast Cell Transcriptome2296-634X10.3389/fcell.2021.670980https://doaj.org/article/eac172fa88e44145b5c660602dfea0162021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fcell.2021.670980/fullhttps://doaj.org/toc/2296-634XMechanistic Target of Rapamycin Complex 2 (mTORC2) regulates placental amino acid and folate transport. However, the role of mTORC2 in modulating other placental functions is largely unexplored. We used a gene array following the silencing of rictor to identify genes regulated by mTORC2 in primary human trophoblast (PHT) cells. Four hundred and nine genes were differentially expressed; 102 genes were down-regulated and 307 up-regulated. Pathway analyses demonstrated that inhibition of mTORC2 resulted in increased expression of genes encoding for pro-inflammatory IL-6, VEGF-A, leptin, and inflammatory signaling (SAPK/JNK). Furthermore, down-regulated genes were functionally enriched in genes involved in angiogenesis (Osteopontin) and multivitamin transport (SLC5A6). In addition, the protein expression of leptin, VEGFA, IL-6 was increased and negatively correlated to mTORC2 signaling in human placentas collected from pregnancies complicated by intrauterine growth restriction (IUGR). In contrast, the protein expression of Osteopontin and SLC5A6 was decreased and positively correlated to mTORC2 signaling in human IUGR placentas. In conclusion, mTORC2 signaling regulates trophoblast expression of genes involved in inflammation, micronutrient transport, and angiogenesis, representing novel links between mTOR signaling and multiple placental functions necessary for fetal growth and development.Fredrick J. RosarioAmy Catherine KellyMadhulika B. GuptaTheresa L. PowellTheresa L. PowellLaura CoxThomas JanssonFrontiers Media S.A.articleplacentamaternal-fetal exchangehumannutrient sensorgene arrayBiology (General)QH301-705.5ENFrontiers in Cell and Developmental Biology, Vol 9 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	placenta maternal-fetal exchange human nutrient sensor gene array Biology (General) QH301-705.5
spellingShingle	placenta maternal-fetal exchange human nutrient sensor gene array Biology (General) QH301-705.5 Fredrick J. Rosario Amy Catherine Kelly Madhulika B. Gupta Theresa L. Powell Theresa L. Powell Laura Cox Thomas Jansson Mechanistic Target of Rapamycin Complex 2 Regulation of the Primary Human Trophoblast Cell Transcriptome
description	Mechanistic Target of Rapamycin Complex 2 (mTORC2) regulates placental amino acid and folate transport. However, the role of mTORC2 in modulating other placental functions is largely unexplored. We used a gene array following the silencing of rictor to identify genes regulated by mTORC2 in primary human trophoblast (PHT) cells. Four hundred and nine genes were differentially expressed; 102 genes were down-regulated and 307 up-regulated. Pathway analyses demonstrated that inhibition of mTORC2 resulted in increased expression of genes encoding for pro-inflammatory IL-6, VEGF-A, leptin, and inflammatory signaling (SAPK/JNK). Furthermore, down-regulated genes were functionally enriched in genes involved in angiogenesis (Osteopontin) and multivitamin transport (SLC5A6). In addition, the protein expression of leptin, VEGFA, IL-6 was increased and negatively correlated to mTORC2 signaling in human placentas collected from pregnancies complicated by intrauterine growth restriction (IUGR). In contrast, the protein expression of Osteopontin and SLC5A6 was decreased and positively correlated to mTORC2 signaling in human IUGR placentas. In conclusion, mTORC2 signaling regulates trophoblast expression of genes involved in inflammation, micronutrient transport, and angiogenesis, representing novel links between mTOR signaling and multiple placental functions necessary for fetal growth and development.
format	article
author	Fredrick J. Rosario Amy Catherine Kelly Madhulika B. Gupta Theresa L. Powell Theresa L. Powell Laura Cox Thomas Jansson
author_facet	Fredrick J. Rosario Amy Catherine Kelly Madhulika B. Gupta Theresa L. Powell Theresa L. Powell Laura Cox Thomas Jansson
author_sort	Fredrick J. Rosario
title	Mechanistic Target of Rapamycin Complex 2 Regulation of the Primary Human Trophoblast Cell Transcriptome
title_short	Mechanistic Target of Rapamycin Complex 2 Regulation of the Primary Human Trophoblast Cell Transcriptome
title_full	Mechanistic Target of Rapamycin Complex 2 Regulation of the Primary Human Trophoblast Cell Transcriptome
title_fullStr	Mechanistic Target of Rapamycin Complex 2 Regulation of the Primary Human Trophoblast Cell Transcriptome
title_full_unstemmed	Mechanistic Target of Rapamycin Complex 2 Regulation of the Primary Human Trophoblast Cell Transcriptome
title_sort	mechanistic target of rapamycin complex 2 regulation of the primary human trophoblast cell transcriptome
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/eac172fa88e44145b5c660602dfea016
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Mechanistic Target of Rapamycin Complex 2 Regulation of the Primary Human Trophoblast Cell Transcriptome

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