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Protein Kinase Bα/Akt1 Regulates Placental Development and Fetal Growth
Open accessAbstract
Protein kinase B alpha (PKB alpha/Akt1) is implicated in the regulation of metabolism, transcription, cell survival, angiogenesis, cell migration, growth, and tumorigenesis. Previously, it was reported that PKB alpha-deficient mice are small with increased neonatal mortality (Cho, H., Thorvaldsen, J. L., Chu, Q., Feng, F., and Birnbaum, M. J. (2001) J. Biol. Chem. 276, 38349-38352 and Chen, W. S., Xu, P. Z., Gottlob, K., Chen, M. L., Sokol, K., Shiyanova, T., Roninson, I., Wenig, W., Suzuki, R., Tobe, K., Kadowaki, T., and Hay, N. (2001) Genes Dev. 15, 2203-2208). Here we show that PKB alpha is widely expressed in placenta including all types of trophoblast and vascular endothelial cells. Pkb alpha-/- placentae display significant hypotrophy, with marked reduction of the decidual basalis and nearly complete loss of glycogen-containing cells in the spongiotrophoblast, and exhibit decreased vascularization. Pkb alpha-/- placentae also show significant reduction of phosphorylation of PKB and endothelial nitric-oxide synthase. These defects may cause placental insufficiency, fetal growth impairment, and neonatal mortality. These data represent the first evidence for the role of PKB alpha and endothelial nitricoxide synthase in regulating placental development and provide an animal model for intrauterine growth retardation.
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“Disruption of just Akt1 causes placental and fetal growth restriction in the mouse, with a particularly severe effect on the development of the glycogen cells (592).”
From Placental Origins of Chronic Disease (2016) · cites this paper as [592]
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Self-citation
Metadata
- Authors
- Yang, Z.-Z., Tschopp, O., Hemmings-Mieszczak, M., Feng, J., Brodbeck, D., Perentes, E., & Hemmings, B. A.
- Affiliations
- Friedrich Miescher Institute (CH)
- Novartis (Switzerland) (CH)
- Corresponding author
- Hemmings, Brian A.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2003-08
- Volume
- 278
- Issue
- 34
- Pages
- 32124-32131
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2131840335
- Cited by
- 384
- References
- 46
- Citations by year
- 2026: 5 · 2025: 14 · 2024: 10 · 2023: 9 · 2022: 11 · 2021: 14 · 2020: 12 · 2019: 14 · 2018: 10 · 2017: 26 · 2016: 14 · 2015: 23 · 2014: 22 · 2013: 22 · 2012: 20
- FWCI
- 17.35
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- Novartis Pharma
- Topics
- Health Sciences › Medicine › Obstetrics and Gynecology › Pregnancy and preeclampsia studies
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Birth, Development, and Health
- Life Sciences › Immunology and Microbiology › Immunology › Reproductive System and Pregnancy
- Keywords
- AKT1, placental development, fetal growth, trophoblast, spongiotrophoblast, placental vascularization, endothelial nitric oxide synthase, endothelial cell proliferation, fetal growth restriction, neonatal mortality
- MeSH terms
- Amino Acid Sequence, Animals, Base Sequence, Embryonic and Fetal Development, Immunohistochemistry, Molecular Sequence Data, Placentation, Proto-Oncogene Proteins, Blotting, Western, Protein Serine-Threonine Kinases, DNA Primers, Mice, Knockout, Proto-Oncogene Proteins c-akt, Mice
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