journal article
Open Access
Mar 17, 2022
Vitamin D stimulates placental L-type amino acid transporter 1 (LAT1) in preeclampsia
Abstract
AbstractVitamin D insufficiency/deficiency has been linked to an increased risk of preeclampsia. Impaired placental amino acid transport is suggested to contribute to abnormal fetal intrauterine growth in pregnancies complicated by preeclampsia. However, if vitamin D-regulated amino acid transporter is involved in the pathophysiologic mechanism of preeclampsia has not been clarified yet. The aberrant expression of key isoform of L-type amino acid transporter LAT1 was determined by western blot and immunohistochemistry in the placenta from normotensive and preeclamptic pregnancies. The role for vitamin D on placental LAT1 expression was investigated through the exposure of HTR-8/SVneo human trophoblast cells to the biologically active 1,25(OH)2D3 and the oxidative stress-inducer cobalt chloride (CoCl2). Our results showed that placental LAT1 expression was reduced in women with preeclampsia compared to normotensive pregnancies, which was associated with decreased expression of vitamin D receptor (VDR). 1,25(OH)2D3 significantly upregulated LAT1 expression in placental trophoblasts, and also prevented the decrease of mTOR activity under CoCl2-induced oxidative stress. siRNA targeting VDR significantly attenuated 1,25(OH)2D3-stimulated LAT1 expression and mTOR signaling activity. Moreover, treatment of rapamycin specifically inhibited the activity of mTOR signaling and resulted in decrease of LAT1 expression. In conclusion, LAT1 expression was downregulated in the placenta from women with preeclampsia. 1,25(OH)2D3/VDR could stimulate LAT1 expression, which was likely mediated by mTOR signaling in placental trophoblasts. Regulation on placental amino acid transport may be one of the mechanisms by which vitamin D affects fetal growth in preeclampsia.
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References
Details
- Published
- Mar 17, 2022
- Vol/Issue
- 12(1)
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Authors
Funding
National Natural Science Foundation of China
Award: 82001577
China Postdoctoral Fund
Award: 2018M640304
Heilongjiang Postdoctoral Foundation
Award: LBH-Z18108
University Nursing Program for Young Scholars with Creative Talents in Heilongjiang Province
Award: UNPYSCT-2018054
Cite This Article
Xiaotong Jia, Yang Cao, Lingyu Ye, et al. (2022). Vitamin D stimulates placental L-type amino acid transporter 1 (LAT1) in preeclampsia. Scientific Reports, 12(1). https://doi.org/10.1038/s41598-022-08641-y
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