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YAP Is Decreased in Preeclampsia and Regulates Invasion and Apoptosis of HTR-8/SVneo.
Reprod Sci 2018; 25(9):1382-1393RS

Abstract

Preeclampsia (PE) is a gestational disorder with hypertension and proteinuria leading to maternal and fetal morbidity and mortality. Yes-associated protein (YAP), a transcription coactivator of Hippo pathway, was identified as an oncoprotein participated in tumorigenesis. However, the effect of YAP on trophoblast has not been investigated. In our study, YAP expression levels in first-trimester, full-term, and PE placentas were detected using quantitative real-time polymerase chain reaction (PCR), Western blot assays, and immunohistochemistry. Yes-associated protein expression was also detected in BeWo and HTR-8/SVneo. Overexpression plasmid and YAP small interfering RNA were introduced into trophoblast cells. Furthermore, we utilized a Transwell invasion assay, flow cytometry, and Cell Counting Kit-8 analysis to examine the role of YAP in the invasion, apoptosis, and proliferation of HTR-8/SVneo trophoblast cells. The result showed that both YAP messenger RNA (mRNA) and protein expression levels were less in preeclamptic placentas. Yes-associated protein mRNA and protein expression levels were more highly expressed in BeWo. Yes-associated protein enhanced cell invasion, reduced the cellular apoptotic response, and had no effect on proliferation. In addition, the overexpression of YAP activated the expression of caudal-related homeobox transcription factor 2 (CDX2), whereas reduced expression of YAP inhibited the expression of CDX2. Our results demonstrate that decreased YAP levels may contribute to the development of PE by regulating trophoblast invasion and apoptosis involving regulation of CDX2. Collectively, we proposed decreased YAP may contribute to trophoblast dysfunction, which suggests it might represent a prognostic biomarker and therapeutic target for PE.

Authors+Show Affiliations

1 Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China. 2 Key Laboratory of Maternal-Fetal Medicine, China Medical University, Shenyang, Liaoning Province, China. 3 Key Laboratory of Obstetrics and Gynecology of Higher Education, China Medical University, Shenyang, Liaoning Province, China.1 Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China. 2 Key Laboratory of Maternal-Fetal Medicine, China Medical University, Shenyang, Liaoning Province, China. 3 Key Laboratory of Obstetrics and Gynecology of Higher Education, China Medical University, Shenyang, Liaoning Province, China.1 Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China. 2 Key Laboratory of Maternal-Fetal Medicine, China Medical University, Shenyang, Liaoning Province, China. 3 Key Laboratory of Obstetrics and Gynecology of Higher Education, China Medical University, Shenyang, Liaoning Province, China.1 Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China. 2 Key Laboratory of Maternal-Fetal Medicine, China Medical University, Shenyang, Liaoning Province, China. 3 Key Laboratory of Obstetrics and Gynecology of Higher Education, China Medical University, Shenyang, Liaoning Province, China.1 Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China. 2 Key Laboratory of Maternal-Fetal Medicine, China Medical University, Shenyang, Liaoning Province, China. 3 Key Laboratory of Obstetrics and Gynecology of Higher Education, China Medical University, Shenyang, Liaoning Province, China.1 Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China. 2 Key Laboratory of Maternal-Fetal Medicine, China Medical University, Shenyang, Liaoning Province, China. 3 Key Laboratory of Obstetrics and Gynecology of Higher Education, China Medical University, Shenyang, Liaoning Province, China.1 Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China. 2 Key Laboratory of Maternal-Fetal Medicine, China Medical University, Shenyang, Liaoning Province, China. 3 Key Laboratory of Obstetrics and Gynecology of Higher Education, China Medical University, Shenyang, Liaoning Province, China.1 Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China. 2 Key Laboratory of Maternal-Fetal Medicine, China Medical University, Shenyang, Liaoning Province, China. 3 Key Laboratory of Obstetrics and Gynecology of Higher Education, China Medical University, Shenyang, Liaoning Province, China.1 Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China. 2 Key Laboratory of Maternal-Fetal Medicine, China Medical University, Shenyang, Liaoning Province, China. 3 Key Laboratory of Obstetrics and Gynecology of Higher Education, China Medical University, Shenyang, Liaoning Province, China.

Pub Type(s)

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

Language

eng

PubMed ID

29303055

Citation

Sun, Man, et al. "YAP Is Decreased in Preeclampsia and Regulates Invasion and Apoptosis of HTR-8/SVneo." Reproductive Sciences (Thousand Oaks, Calif.), vol. 25, no. 9, 2018, pp. 1382-1393.
Sun M, Na Q, Huang L, et al. YAP Is Decreased in Preeclampsia and Regulates Invasion and Apoptosis of HTR-8/SVneo. Reprod Sci. 2018;25(9):1382-1393.
Sun, M., Na, Q., Huang, L., Song, G., Jin, F., Li, Y., ... Qiao, C. (2018). YAP Is Decreased in Preeclampsia and Regulates Invasion and Apoptosis of HTR-8/SVneo. Reproductive Sciences (Thousand Oaks, Calif.), 25(9), pp. 1382-1393. doi:10.1177/1933719117746784.
Sun M, et al. YAP Is Decreased in Preeclampsia and Regulates Invasion and Apoptosis of HTR-8/SVneo. Reprod Sci. 2018;25(9):1382-1393. PubMed PMID: 29303055.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - YAP Is Decreased in Preeclampsia and Regulates Invasion and Apoptosis of HTR-8/SVneo. AU - Sun,Man, AU - Na,Quan, AU - Huang,Ling, AU - Song,Guiyu, AU - Jin,Feng, AU - Li,Yuanyuan, AU - Hou,Yue, AU - Kang,Danyang, AU - Qiao,Chong, Y1 - 2018/01/05/ PY - 2018/1/6/pubmed PY - 2018/11/28/medline PY - 2018/1/6/entrez KW - CDX2 KW - HTR-8/SVneo KW - YAP KW - preeclampsia KW - trophoblast SP - 1382 EP - 1393 JF - Reproductive sciences (Thousand Oaks, Calif.) JO - Reprod Sci VL - 25 IS - 9 N2 - Preeclampsia (PE) is a gestational disorder with hypertension and proteinuria leading to maternal and fetal morbidity and mortality. Yes-associated protein (YAP), a transcription coactivator of Hippo pathway, was identified as an oncoprotein participated in tumorigenesis. However, the effect of YAP on trophoblast has not been investigated. In our study, YAP expression levels in first-trimester, full-term, and PE placentas were detected using quantitative real-time polymerase chain reaction (PCR), Western blot assays, and immunohistochemistry. Yes-associated protein expression was also detected in BeWo and HTR-8/SVneo. Overexpression plasmid and YAP small interfering RNA were introduced into trophoblast cells. Furthermore, we utilized a Transwell invasion assay, flow cytometry, and Cell Counting Kit-8 analysis to examine the role of YAP in the invasion, apoptosis, and proliferation of HTR-8/SVneo trophoblast cells. The result showed that both YAP messenger RNA (mRNA) and protein expression levels were less in preeclamptic placentas. Yes-associated protein mRNA and protein expression levels were more highly expressed in BeWo. Yes-associated protein enhanced cell invasion, reduced the cellular apoptotic response, and had no effect on proliferation. In addition, the overexpression of YAP activated the expression of caudal-related homeobox transcription factor 2 (CDX2), whereas reduced expression of YAP inhibited the expression of CDX2. Our results demonstrate that decreased YAP levels may contribute to the development of PE by regulating trophoblast invasion and apoptosis involving regulation of CDX2. Collectively, we proposed decreased YAP may contribute to trophoblast dysfunction, which suggests it might represent a prognostic biomarker and therapeutic target for PE. SN - 1933-7205 UR - https://www.unboundmedicine.com/medline/citation/29303055/YAP_Is_Decreased_in_Preeclampsia_and_Regulates_Invasion_and_Apoptosis_of_HTR_8/SVneo_ L2 - http://journals.sagepub.com/doi/full/10.1177/1933719117746784?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -