ArticlePhysiological reports2015
TNF-α stimulates System A amino acid transport in primary human trophoblast cells mediated by p38 MAPK signaling.
Article in Physiological reports, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 43 citations in OpenAlex.
- The placental tryptophan pathway across gestation: implications for pregnancy outcomes.Human reproduction update · 2026Review
- Gestational High-Fat Diet Drives Premature Differentiation of Orexigenic Neurons and Reactivity of Astrocytes in the Fetal Rat Lateral Hypothalamus.Brain sciences · 2025Article
- Regulation of placental amino acid transport in health and disease.Acta physiologica (Oxford, England) · 2024Review
- Epigenetic modifications of placenta in women with gestational diabetes mellitus and their offspring.World journal of diabetes · 2024Review
- Human placental cells are resistant to SARS-CoV-2 infection and replication.Wellcome open research · 2024Article
- Made in the Womb: Maternal Programming of Offspring Cardiovascular Function by an Obesogenic Womb.Metabolites · 2023Review
- Maternal immune activation and role of placenta in the prenatal programming of neurodevelopmental disorders.Neuronal signaling · 2023Review
- Study on the mechanism of oral administration of tetrandrine during neoadjuvant chemotherapy for colon cancer.Oncology letters · 2023Article
- Influence of Adipose Tissue on Early Metabolic Programming: Conditioning Factors and Early Screening.Diagnostics (Basel, Switzerland) · 2023Review
- Maternal Protein Restriction in Rats Alters Postnatal Growth and Brain Lipid Sensing in Female Offspring.Nutrients · 2023Article
- Expression of nutrient transporters in placentas affected by gestational diabetes: role of leptin.Frontiers in endocrinology · 2023Review
- Maternal immune activation in rats induces dysfunction of placental leucine transport and alters fetal brain growth.Clinical science (London, England : 1979) · 2022Article
- Nesfatin-1 alleviates high glucose/high lipid-induced injury of trophoblast cells during gestational diabetes mellitus.Bioengineered · 2021Article
- Placental Function and the Development of Fetal Overgrowth and Fetal Growth Restriction.Obstetrics and gynecology clinics of North America · 2021Review
- Efficacy of Low Molecular Heparin on Preeclampsia by Inhibiting Apoptosis of Trophoblasts via the p38MAPK Signaling Pathway.Computational and mathematical methods in medicine · 2021Article
- Placental function in maternal obesity.Clinical science (London, England : 1979) · 2020Review
- No evidence of attenuation of placental insulin-stimulated Akt phosphorylation and amino acid transport in maternal obesity and gestational diabetes mellitus.American journal of physiology. Endocrinology and metabolism · 2019Article
- Apelin is a novel regulator of human trophoblast amino acid transport.American journal of physiology. Endocrinology and metabolism · 2019Article
- Programming of Vascular Dysfunction in the Intrauterine Milieu of Diabetic Pregnancies.International journal of molecular sciences · 2018Review
- Placental Ras Regulates Inflammation Associated with Maternal Obesity.Mediators of inflammation · 2018Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Maternal obesity and gestational diabetes mellitus (GDM) increase the risk of delivering infants that are large for gestational age with greater adiposity, who are prone to the development of metabolic disease in childhood and beyond. These maternal conditions are also associated with increased levels of the proinflammatory cytokine TNF-α in maternal tissues and the placenta. Recent evidence suggests that changes in placental amino acid transport contribute to altered fetal growth. TNF-α was previously shown to stimulate System A amino acid transport in primary human trophoblasts (PHTs), however the molecular mechanisms remain unknown. In this study, we tested the hypothesis that TNF-α regulates amino acid uptake in cultured PHTs by a mitogen-activated protein kinase (MAPK)-dependent mechanism. Treatment of PHTs with TNF-α significantly increased System A amino acid transport, as well as Erk and p38 MAPK signaling. Pharmacological antagonism of p38, but not Erk MAPK activity, inhibited TNF-α stimulated System A activity. Silencing of p38 MAPK using siRNA transfections prevented TNF-α stimulated System A transport in PHTs. TNF-α significantly increased the protein expression of System A transporters SNAT1 and SNAT2, but did not affect their mRNA expression. The effects of TNF-α on SNAT1 and SNAT2 protein expression were reversed by p38 MAPK siRNA silencing. In conclusion, TNF-α regulates System A activity through increased SNAT1 and SNAT2 transporter protein expression in PHTs. These findings suggest that p38 MAPK may represent a critical mechanistic link between elevated proinflammatory cytokines and increased placental amino acid transport in obese and GDM pregnancies associated with fetal overgrowth.
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