AMPK Knockdown in Placental Trophoblast Cells Results in Altered Morphology and Function
Open accessAbstract
The placenta is a transient organ that develops upon the initiation of pregnancy and is essential for embryonic development and fetal survival. The rodent placenta consists of distinct lineages and includes cell types that are analogous to those that make up the human placenta. Trophoblast cells within the labyrinth layer, which lies closest to the fetus, fuse and come in contact with maternal blood, thus facilitating nutrient and waste exchange between the mother and the baby. Abnormalities of the placenta may occur as a result of cellular stress and have been associated with pregnancy-associated disorders: such as preeclampsia, intrauterine growth restriction, and placental insufficiency. Cellular stress has also been shown to alter proliferation and differentiation rates of trophoblast cells. This stress response is important for cell survival and ensures continued placental functionality. AMP-activated protein kinase is an important sensor of cellular metabolism and stress. To study the role of AMPK in the trophoblast cells, we used RNA interference to simultaneously knockdown levels of both the AMPK alpha isoforms, AMPKα1 and AMPKα2. SM10 trophoblast progenitor cells were transduced with AMPKα1/2 shRNA and stable clones were established to analyze the effects of AMPK knockdown on important cellular functions. Our results indicate that a reduction in AMPK levels causes alterations in cell morphology, growth rate, and nutrient transport, thus identifying an important role for AMPK in the regulation of placental trophoblast differentiation.
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Knockdown of AMPKα1 and AMPKα2 inhibits cell proliferation and cytokine-induced differentiation.
“In addition, knockdown inhibits cell proliferation and cytokine-induced differentiation.”
From Placental Origins of Chronic Disease (2016) · cites this paper as [93]
Knockdown of the isoforms AMPKα1 and AMPKα2 in murine SM10 trophoblast progenitor cells affects cell nutrient transport, inhibiting expression of Glut3 and blocking translocation of the protein to the cell surface, but increasing the activity of system A transporters.
“Knockdown of the isoforms AMPKα1 and AMPKα2 in murine SM10 trophoblast progenitor cells has been shown to affect cell nutrient transport, inhibiting expression of Glut3 and blocking translocation of the protein to the cell surface, but increasing the activity of system A transporters(93).”
From Placental Origins of Chronic Disease (2016) · cites this paper as [93]
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References 52 · Cited by 56
- Authors
- Carey, E. A. K., Albers, R. E., Doliboa, S. R., Hughes, M., Wyatt, C. N., Natale, D. R. C., & Brown, T. L.
- Affiliations
- Wright State University (US)
- University of Calgary (CA)
- Corresponding author
- Brown, Thomas L.
- Venue
- Stem Cells and Development
- Publisher
- SAGE Publications
- Published
- 2014-07-08
- Volume
- 23
- Issue
- 23
- Pages
- 2921-2930
- ISSN
- 1525-8165 (ISSN-L)
- 1547-3287
- 1557-8534
- PMC
- PMC4235592
- OpenAlex
- W272346991
- Cited by
- 56
- References
- 52
- Citations by year
- 2026: 3 · 2025: 6 · 2024: 4 · 2023: 3 · 2022: 7 · 2021: 7 · 2020: 8 · 2019: 4 · 2018: 5 · 2017: 4 · 2016: 5
- FWCI
- 3.19
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Stem Cells and Development (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r01hl091836-04)
- National Heart, Lung, and Blood Institute (R01 HL091836)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01HD059969)
- Topics
- Health Sciences › Medicine › Obstetrics and Gynecology › Pregnancy and preeclampsia studies
- Life Sciences › Immunology and Microbiology › Immunology › Reproductive System and Pregnancy
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Keywords
- AMPK, trophoblast, placenta, trophoblast differentiation, cell morphology, cell growth, nutrient transport, cellular stress response, preeclampsia, fetal growth restriction, placental insufficiency
- MeSH terms
- Animals, Cell Differentiation, Stem Cells, Trophoblasts, Cell Proliferation, Mice, AMP-Activated Protein Kinases, Gene Knockdown Techniques
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