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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)<jats:sub>2<\/jats:sub>D<jats:sub>3<\/jats:sub> and the oxidative stress-inducer cobalt chloride (CoCl<jats:sub>2<\/jats:sub>). 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)<jats:sub>2<\/jats:sub>D<jats:sub>3<\/jats:sub> significantly upregulated LAT1 expression in placental trophoblasts, and also prevented the decrease of mTOR activity under CoCl<jats:sub>2<\/jats:sub>-induced oxidative stress. siRNA targeting VDR significantly attenuated 1,25(OH)<jats:sub>2<\/jats:sub>D<jats:sub>3<\/jats:sub>-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)<jats:sub>2<\/jats:sub>D<jats:sub>3<\/jats:sub>\/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.<\/jats:p>","DOI":"10.1038\/s41598-022-08641-y","type":"journal-article","created":{"date-parts":[[2022,3,17]],"date-time":"2022-03-17T19:08:10Z","timestamp":1647544090000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Vitamin D stimulates placental L-type amino acid transporter 1 (LAT1) in preeclampsia"],"prefix":"10.1038","volume":"12","author":[{"given":"Xiaotong","family":"Jia","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Cao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lingyu","family":"Ye","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xueqing","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yujia","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaolei","family":"Yuan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunmei","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,3,17]]},"reference":[{"key":"8641_CR1","doi-asserted-by":"publisher","first-page":"1102","DOI":"10.2215\/CJN.12081115","volume":"11","author":"E Phipps","year":"2016","unstructured":"Phipps, E. et al. 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