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Inactivation of Yes-Associated Protein Mediates Trophoblast Dysfunction: A New Mechanism of Pregnancy Loss Associated with Anti-Phospholipid Antibodies?
Pregnancy morbidity induced by anti-phospholipid antibodies (aPL+/PM+) is mainly thought to arise from placental abnormalities. We attempted to investigate the effect of aPL on the activity of Yes-associated protein (YAP) in the trophoblast and how YAP regulated human trophoblasts function. Thus, HT...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9776042/ https://www.ncbi.nlm.nih.gov/pubmed/36552052 http://dx.doi.org/10.3390/biomedicines10123296 |
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author | Huang, Zengshu Tang, Zhijing Guan, Haiyun Leung, Wingting Wang, Lu Xia, Hexia Zhang, Wei |
author_facet | Huang, Zengshu Tang, Zhijing Guan, Haiyun Leung, Wingting Wang, Lu Xia, Hexia Zhang, Wei |
author_sort | Huang, Zengshu |
collection | PubMed |
description | Pregnancy morbidity induced by anti-phospholipid antibodies (aPL+/PM+) is mainly thought to arise from placental abnormalities. We attempted to investigate the effect of aPL on the activity of Yes-associated protein (YAP) in the trophoblast and how YAP regulated human trophoblasts function. Thus, HTR-8 cells were treated with IgG purified from aPL+/PM+ women or normal controls. We found that aPL+/PM+ IgG impacted YAP activity via abrogating YAP expression. Further investigation of the anti-β2GPI-IgG/β2GPI complex showed an inhibition of nuclear YAP level and translocation in a dose-dependent manner, which might be rescued by progesterone in HTR-8 cells. YAP overexpression or knockdown HTR-8 cells were established for the evaluation of cell function and related gene expression in vitro. Loss of YAP arrested cell cycles in the G2/M phase, accelerated cell apoptosis by increasing the ratio of Bax/Bcl2, and disrupted MMP2/9-mediated cell migration and angiogenesis tube formation by VEGF. These findings support a new mechanism of PM associated with aPL through which YAP inactivation induced by aPL perturbs the trophoblast cell cycle, apoptosis, migration, and angiogenesis, finally developing into pregnancy failure. |
format | Online Article Text |
id | pubmed-9776042 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-97760422022-12-23 Inactivation of Yes-Associated Protein Mediates Trophoblast Dysfunction: A New Mechanism of Pregnancy Loss Associated with Anti-Phospholipid Antibodies? Huang, Zengshu Tang, Zhijing Guan, Haiyun Leung, Wingting Wang, Lu Xia, Hexia Zhang, Wei Biomedicines Article Pregnancy morbidity induced by anti-phospholipid antibodies (aPL+/PM+) is mainly thought to arise from placental abnormalities. We attempted to investigate the effect of aPL on the activity of Yes-associated protein (YAP) in the trophoblast and how YAP regulated human trophoblasts function. Thus, HTR-8 cells were treated with IgG purified from aPL+/PM+ women or normal controls. We found that aPL+/PM+ IgG impacted YAP activity via abrogating YAP expression. Further investigation of the anti-β2GPI-IgG/β2GPI complex showed an inhibition of nuclear YAP level and translocation in a dose-dependent manner, which might be rescued by progesterone in HTR-8 cells. YAP overexpression or knockdown HTR-8 cells were established for the evaluation of cell function and related gene expression in vitro. Loss of YAP arrested cell cycles in the G2/M phase, accelerated cell apoptosis by increasing the ratio of Bax/Bcl2, and disrupted MMP2/9-mediated cell migration and angiogenesis tube formation by VEGF. These findings support a new mechanism of PM associated with aPL through which YAP inactivation induced by aPL perturbs the trophoblast cell cycle, apoptosis, migration, and angiogenesis, finally developing into pregnancy failure. MDPI 2022-12-19 /pmc/articles/PMC9776042/ /pubmed/36552052 http://dx.doi.org/10.3390/biomedicines10123296 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Huang, Zengshu Tang, Zhijing Guan, Haiyun Leung, Wingting Wang, Lu Xia, Hexia Zhang, Wei Inactivation of Yes-Associated Protein Mediates Trophoblast Dysfunction: A New Mechanism of Pregnancy Loss Associated with Anti-Phospholipid Antibodies? |
title | Inactivation of Yes-Associated Protein Mediates Trophoblast Dysfunction: A New Mechanism of Pregnancy Loss Associated with Anti-Phospholipid Antibodies? |
title_full | Inactivation of Yes-Associated Protein Mediates Trophoblast Dysfunction: A New Mechanism of Pregnancy Loss Associated with Anti-Phospholipid Antibodies? |
title_fullStr | Inactivation of Yes-Associated Protein Mediates Trophoblast Dysfunction: A New Mechanism of Pregnancy Loss Associated with Anti-Phospholipid Antibodies? |
title_full_unstemmed | Inactivation of Yes-Associated Protein Mediates Trophoblast Dysfunction: A New Mechanism of Pregnancy Loss Associated with Anti-Phospholipid Antibodies? |
title_short | Inactivation of Yes-Associated Protein Mediates Trophoblast Dysfunction: A New Mechanism of Pregnancy Loss Associated with Anti-Phospholipid Antibodies? |
title_sort | inactivation of yes-associated protein mediates trophoblast dysfunction: a new mechanism of pregnancy loss associated with anti-phospholipid antibodies? |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9776042/ https://www.ncbi.nlm.nih.gov/pubmed/36552052 http://dx.doi.org/10.3390/biomedicines10123296 |
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