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CDX1 restricts the invasion of HTR-8/SVneo trophoblast cells by inhibiting MMP-9 expression.
Placenta 2014; 35(7):450-4P

Abstract

INTRODUCTION

Pathogenesis of early-onset preeclampsia (PE) is generally recognized by impaired trophoblast invasion of the myometrial arteries, which results in placental insufficiency. Recently, we reported that CDX1 is hypermethylated in the human preeclampsia placenta. However, whether CDX1 participates in trophoblast invasion has not been clearly elucidated.

METHODS

We investigated the function of CDX1 in the extravillous trophoblast cell line HTR-8/SVneo using stable transfection of CDX1. Using a CDX1 stable transfected cell line, we determined the cell invasion using a QCM ECMatrix 24-well kit. The cell viability was detected using an MTT (3-[4, 5-dimethylthiazol-2-yl]-2, 5-diphenyltetrazolium bromide) assay. Quantitative RT-PCR and western blotting analyses were performed to examine the changes in the expression of downstream target genes and proteins. To disrupt PI3K/AKT signaling, we used the PI3K inhibitor perifosine.

RESULTS

Cell invasion assays demonstrated that CDX1 restricts trophoblast cell invasiveness. In contrast, quantification of cumulative cell numbers revealed that CDX1 did not affect cell proliferation. Western blotting analysis and quantitative real time PCR demonstrated that MMP-9 expression was reduced, whereas TIMP-1 expression was increased in CDX1-overexpressed cells. However, overexpression of CDX1 did not affect PI3K/AKT signaling in HTR-8/SVneo trophoblast cells. In contrast, CDX1 was regulated by the PI3K/AKT signaling pathway.

CONCLUSIONS

Altogether, we found that in trophoblast cells, CDX1 reduced invasion independently of the PI3K/AKT signaling pathway. Furthermore, CDX1 functions in concert with PI3K/AKT signaling to regulate trophoblast invasion. We concluded that CDX1 restricts the invasion of HTR-8/SVneo trophoblast cells by inhibiting MMP-9 expression independently of the PI3K/AKT pathway.

Authors+Show Affiliations

Department of Obstetrics, Nanjing Medical University Affiliated Nanjing Maternal and Child Health Hospital, Tianfei Street, Nanjing 210004, China.Department of Obstetrics, Nanjing Medical University Affiliated Nanjing Maternal and Child Health Hospital, Tianfei Street, Nanjing 210004, China.Department of Plastic Surgery, Nanjing Medical University Affiliated Nanjing Maternal and Child Health Hospital, Tianfei Street, Nanjing 210004, China. Electronic address: lijingyun175@gmail.com.Nanjing Maternal and Child Health Medical Institute, Nanjing Medical University Affiliated Nanjing Maternal and Child Health Hospital, Tianfei Street, Nanjing 210004, China.Department of Obstetrics, Nanjing Medical University Affiliated Nanjing Maternal and Child Health Hospital, Tianfei Street, Nanjing 210004, China. Electronic address: wangxin_dr@163.com.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

24836459

Citation

Jia, R Z., et al. "CDX1 Restricts the Invasion of HTR-8/SVneo Trophoblast Cells By Inhibiting MMP-9 Expression." Placenta, vol. 35, no. 7, 2014, pp. 450-4.
Jia RZ, Rui C, Li JY, et al. CDX1 restricts the invasion of HTR-8/SVneo trophoblast cells by inhibiting MMP-9 expression. Placenta. 2014;35(7):450-4.
Jia, R. Z., Rui, C., Li, J. Y., Cui, X. W., & Wang, X. (2014). CDX1 restricts the invasion of HTR-8/SVneo trophoblast cells by inhibiting MMP-9 expression. Placenta, 35(7), pp. 450-4. doi:10.1016/j.placenta.2014.04.011.
Jia RZ, et al. CDX1 Restricts the Invasion of HTR-8/SVneo Trophoblast Cells By Inhibiting MMP-9 Expression. Placenta. 2014;35(7):450-4. PubMed PMID: 24836459.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - CDX1 restricts the invasion of HTR-8/SVneo trophoblast cells by inhibiting MMP-9 expression. AU - Jia,R Z, AU - Rui,C, AU - Li,J Y, AU - Cui,X W, AU - Wang,X, Y1 - 2014/05/01/ PY - 2013/10/15/received PY - 2014/04/10/revised PY - 2014/04/21/accepted PY - 2014/5/20/entrez PY - 2014/5/20/pubmed PY - 2015/5/12/medline KW - CDX1 KW - HTR-8/SVneo KW - MMP-9 KW - Preeclampsia KW - Trophoblast invasion SP - 450 EP - 4 JF - Placenta JO - Placenta VL - 35 IS - 7 N2 - INTRODUCTION: Pathogenesis of early-onset preeclampsia (PE) is generally recognized by impaired trophoblast invasion of the myometrial arteries, which results in placental insufficiency. Recently, we reported that CDX1 is hypermethylated in the human preeclampsia placenta. However, whether CDX1 participates in trophoblast invasion has not been clearly elucidated. METHODS: We investigated the function of CDX1 in the extravillous trophoblast cell line HTR-8/SVneo using stable transfection of CDX1. Using a CDX1 stable transfected cell line, we determined the cell invasion using a QCM ECMatrix 24-well kit. The cell viability was detected using an MTT (3-[4, 5-dimethylthiazol-2-yl]-2, 5-diphenyltetrazolium bromide) assay. Quantitative RT-PCR and western blotting analyses were performed to examine the changes in the expression of downstream target genes and proteins. To disrupt PI3K/AKT signaling, we used the PI3K inhibitor perifosine. RESULTS: Cell invasion assays demonstrated that CDX1 restricts trophoblast cell invasiveness. In contrast, quantification of cumulative cell numbers revealed that CDX1 did not affect cell proliferation. Western blotting analysis and quantitative real time PCR demonstrated that MMP-9 expression was reduced, whereas TIMP-1 expression was increased in CDX1-overexpressed cells. However, overexpression of CDX1 did not affect PI3K/AKT signaling in HTR-8/SVneo trophoblast cells. In contrast, CDX1 was regulated by the PI3K/AKT signaling pathway. CONCLUSIONS: Altogether, we found that in trophoblast cells, CDX1 reduced invasion independently of the PI3K/AKT signaling pathway. Furthermore, CDX1 functions in concert with PI3K/AKT signaling to regulate trophoblast invasion. We concluded that CDX1 restricts the invasion of HTR-8/SVneo trophoblast cells by inhibiting MMP-9 expression independently of the PI3K/AKT pathway. SN - 1532-3102 UR - https://www.unboundmedicine.com/medline/citation/24836459/CDX1_restricts_the_invasion_of_HTR_8/SVneo_trophoblast_cells_by_inhibiting_MMP_9_expression_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0143-4004(14)00163-5 DB - PRIME DP - Unbound Medicine ER -