Cargando…
WNT3 hypomethylation counteracts low activity of the Wnt signaling pathway in the placenta of preeclampsia
Preeclampsia is a hypertensive disorder of pregnancy. Many studies have shown that epigenetic mechanisms may play a role in preeclampsia. Moreover, our previous study indicated that the differentially methylated genes in preeclampsia were enriched in the Wnt/β-catenin signaling pathway. This study a...
Autores principales: | , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer International Publishing
2021
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8558176/ https://www.ncbi.nlm.nih.gov/pubmed/34608506 http://dx.doi.org/10.1007/s00018-021-03941-4 |
_version_ | 1784592497538760704 |
---|---|
author | Zhang, Linlin Sang, Min Li, Ying Li, Yingying Yuan, Erfeng Yang, Lijun Shi, Wenli Yuan, Yangyang Yang, Bo Yang, Peifeng Yuan, Enwu |
author_facet | Zhang, Linlin Sang, Min Li, Ying Li, Yingying Yuan, Erfeng Yang, Lijun Shi, Wenli Yuan, Yangyang Yang, Bo Yang, Peifeng Yuan, Enwu |
author_sort | Zhang, Linlin |
collection | PubMed |
description | Preeclampsia is a hypertensive disorder of pregnancy. Many studies have shown that epigenetic mechanisms may play a role in preeclampsia. Moreover, our previous study indicated that the differentially methylated genes in preeclampsia were enriched in the Wnt/β-catenin signaling pathway. This study aimed to identify differentially methylated Wnt/β-catenin signaling pathway genes in the preeclamptic placenta and to study the roles of these genes in trophoblast cells in vitro. Using an Illumina Infinium HumanMethylation 850 K BeadChip, we found that the Wnt signaling pathway was globally hypermethylated in the preeclamptic group compared with the term birth group, but hypomethylated in the preeclamptic group compared with the preterm birth group. Among all Wnt/β-catenin signaling pathway factors, WNT3 was the most significantly differentially expressed gene and was hypomethylated in the preeclamptic group compared to the nonhypertensive groups, namely, the preterm birth group and term birth group. This result was confirmed by pyrosequencing. Through quantitative real-time PCR and western blot analysis, the WNT3 gene was found to be highly expressed in preeclamptic placental tissues, in contrast to other WNT factors, which were previously reported to be expressed at low levels in placental tissues. Additionally, in the HTR8/SVneo cell line, knockdown of WNT3 suppressed the Wnt/β-catenin signaling pathway, consistent with the findings for other WNT factors. These results prompted us to speculate that the WNT3 gene counteracts the low activation state of the Wnt signaling pathway in the preeclamptic placenta through methylation modification. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00018-021-03941-4. |
format | Online Article Text |
id | pubmed-8558176 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Springer International Publishing |
record_format | MEDLINE/PubMed |
spelling | pubmed-85581762021-11-15 WNT3 hypomethylation counteracts low activity of the Wnt signaling pathway in the placenta of preeclampsia Zhang, Linlin Sang, Min Li, Ying Li, Yingying Yuan, Erfeng Yang, Lijun Shi, Wenli Yuan, Yangyang Yang, Bo Yang, Peifeng Yuan, Enwu Cell Mol Life Sci Original Article Preeclampsia is a hypertensive disorder of pregnancy. Many studies have shown that epigenetic mechanisms may play a role in preeclampsia. Moreover, our previous study indicated that the differentially methylated genes in preeclampsia were enriched in the Wnt/β-catenin signaling pathway. This study aimed to identify differentially methylated Wnt/β-catenin signaling pathway genes in the preeclamptic placenta and to study the roles of these genes in trophoblast cells in vitro. Using an Illumina Infinium HumanMethylation 850 K BeadChip, we found that the Wnt signaling pathway was globally hypermethylated in the preeclamptic group compared with the term birth group, but hypomethylated in the preeclamptic group compared with the preterm birth group. Among all Wnt/β-catenin signaling pathway factors, WNT3 was the most significantly differentially expressed gene and was hypomethylated in the preeclamptic group compared to the nonhypertensive groups, namely, the preterm birth group and term birth group. This result was confirmed by pyrosequencing. Through quantitative real-time PCR and western blot analysis, the WNT3 gene was found to be highly expressed in preeclamptic placental tissues, in contrast to other WNT factors, which were previously reported to be expressed at low levels in placental tissues. Additionally, in the HTR8/SVneo cell line, knockdown of WNT3 suppressed the Wnt/β-catenin signaling pathway, consistent with the findings for other WNT factors. These results prompted us to speculate that the WNT3 gene counteracts the low activation state of the Wnt signaling pathway in the preeclamptic placenta through methylation modification. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00018-021-03941-4. Springer International Publishing 2021-10-04 2021 /pmc/articles/PMC8558176/ /pubmed/34608506 http://dx.doi.org/10.1007/s00018-021-03941-4 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Original Article Zhang, Linlin Sang, Min Li, Ying Li, Yingying Yuan, Erfeng Yang, Lijun Shi, Wenli Yuan, Yangyang Yang, Bo Yang, Peifeng Yuan, Enwu WNT3 hypomethylation counteracts low activity of the Wnt signaling pathway in the placenta of preeclampsia |
title | WNT3 hypomethylation counteracts low activity of the Wnt signaling pathway in the placenta of preeclampsia |
title_full | WNT3 hypomethylation counteracts low activity of the Wnt signaling pathway in the placenta of preeclampsia |
title_fullStr | WNT3 hypomethylation counteracts low activity of the Wnt signaling pathway in the placenta of preeclampsia |
title_full_unstemmed | WNT3 hypomethylation counteracts low activity of the Wnt signaling pathway in the placenta of preeclampsia |
title_short | WNT3 hypomethylation counteracts low activity of the Wnt signaling pathway in the placenta of preeclampsia |
title_sort | wnt3 hypomethylation counteracts low activity of the wnt signaling pathway in the placenta of preeclampsia |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8558176/ https://www.ncbi.nlm.nih.gov/pubmed/34608506 http://dx.doi.org/10.1007/s00018-021-03941-4 |
work_keys_str_mv | AT zhanglinlin wnt3hypomethylationcounteractslowactivityofthewntsignalingpathwayintheplacentaofpreeclampsia AT sangmin wnt3hypomethylationcounteractslowactivityofthewntsignalingpathwayintheplacentaofpreeclampsia AT liying wnt3hypomethylationcounteractslowactivityofthewntsignalingpathwayintheplacentaofpreeclampsia AT liyingying wnt3hypomethylationcounteractslowactivityofthewntsignalingpathwayintheplacentaofpreeclampsia AT yuanerfeng wnt3hypomethylationcounteractslowactivityofthewntsignalingpathwayintheplacentaofpreeclampsia AT yanglijun wnt3hypomethylationcounteractslowactivityofthewntsignalingpathwayintheplacentaofpreeclampsia AT shiwenli wnt3hypomethylationcounteractslowactivityofthewntsignalingpathwayintheplacentaofpreeclampsia AT yuanyangyang wnt3hypomethylationcounteractslowactivityofthewntsignalingpathwayintheplacentaofpreeclampsia AT yangbo wnt3hypomethylationcounteractslowactivityofthewntsignalingpathwayintheplacentaofpreeclampsia AT yangpeifeng wnt3hypomethylationcounteractslowactivityofthewntsignalingpathwayintheplacentaofpreeclampsia AT yuanenwu wnt3hypomethylationcounteractslowactivityofthewntsignalingpathwayintheplacentaofpreeclampsia |