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Vitamin D facilitates trophoblast invasion through induction of epithelial‐mesenchymal transition
Author(s) -
Kim Ryang Hee,
Ryu Byung Jun,
Lee Ki Mo,
Han Jae Won,
Lee Sung Ki
Publication year - 2018
Publication title -
american journal of reproductive immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.071
H-Index - 97
eISSN - 1600-0897
pISSN - 1046-7408
DOI - 10.1111/aji.12796
Subject(s) - calcitriol , calcitriol receptor , epithelial–mesenchymal transition , trophoblast , mapk/erk pathway , vitamin d and neurology , signal transduction , cancer research , mesenchymal stem cell , biology , secretion , endocrinology , vitamin d deficiency , preeclampsia , medicine , microbiology and biotechnology , downregulation and upregulation , fetus , pregnancy , placenta , biochemistry , genetics , gene
Problem Vitamin D deficiency increases the risk of developing pregnancy‐related complications, including preeclampsia and small‐for‐gestational‐age infants. Vitamin D was demonstrated to promote the invasiveness of human extravillous trophoblasts ( EVT s). However, whether vitamin D induces the epithelial‐mesenchymal transition ( EMT ) of EVT s remains unclear. Therefore, we investigated whether vitamin D promotes EMT and the related signaling pathways. Method of study In this study, we performed EMT experiments using JAR cells based on the expression of the mesenchymal markers and vitamin D receptor. JAR cells were treated with calcitriol, the active form of vitamin D. Western blotting was performed to evaluate EMT markers and key molecules of signaling pathways. Invasion assays were conducted. Expression and secretion of MMP s were analyzed by real‐time PCR and zymography. Results Calcitriol significantly enhanced EMT and the invasive capability of JAR cells, along with increased expression and secretion of MMP ‐2 and MMP ‐9. Moreover, ERK signaling pathway was activated by calcitriol. The effects of calcitriol were neutralized by ERK signaling blocker. Conclusion Calcitriol facilitated EMT induction and expression of MMP s via ERK signaling pathway, which promoted the invasive capability of EVT s. Further studies are warranted to elucidate the potential application of vitamin D in the prevention of pregnancy complications.