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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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-11-01
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| Series: | Frontiers in Cell and Developmental Biology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcell.2021.670980/full |
| _version_ | 1818839304775925760 |
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| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-19T03:52:10Z |
| format | Article |
| id | doaj.art-eac172fa88e44145b5c660602dfea016 |
| institution | Directory Open Access Journal |
| issn | 2296-634X |
| language | English |
| last_indexed | 2024-12-19T03:52:10Z |
| publishDate | 2021-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cell and Developmental Biology |
| spelling | doaj.art-eac172fa88e44145b5c660602dfea0162022-12-21T20:36:58ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2021-11-01910.3389/fcell.2021.670980670980Mechanistic Target of Rapamycin Complex 2 Regulation of the Primary Human Trophoblast Cell TranscriptomeFredrick J. Rosario0Amy Catherine Kelly1Madhulika B. Gupta2Theresa L. Powell3Theresa L. Powell4Laura Cox5Thomas Jansson6Division of Reproductive Sciences, Department of OB/GYN University of Colorado Anschutz Medical Campus, Aurora, CO, United StatesDivision of Reproductive Sciences, Department of OB/GYN University of Colorado Anschutz Medical Campus, Aurora, CO, United StatesChildren’s Health Research Institute and Department of Pediatrics and Biochemistry, University of Western Ontario, London, ON, CanadaDivision of Reproductive Sciences, Department of OB/GYN University of Colorado Anschutz Medical Campus, Aurora, CO, United StatesSection of Neonatology, Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, CO, United StatesSection of Molecular Medicine, Department of Internal Medicine, Center for Precision Medicine, Wake Forest School of Medicine, Winston-Salem, NC, United StatesDivision of Reproductive Sciences, Department of OB/GYN University of Colorado Anschutz Medical Campus, Aurora, CO, United StatesMechanistic 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.https://www.frontiersin.org/articles/10.3389/fcell.2021.670980/fullplacentamaternal-fetal exchangehumannutrient sensorgene array |
| spellingShingle | 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 Frontiers in Cell and Developmental Biology placenta maternal-fetal exchange human nutrient sensor gene array |
| title | 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_short | 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 |
| topic | placenta maternal-fetal exchange human nutrient sensor gene array |
| url | https://www.frontiersin.org/articles/10.3389/fcell.2021.670980/full |
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