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Volume 10
Issue 12
10.3390/biomedicines10123296
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Article

Inactivation of Yes-Associated Protein Mediates Trophoblast Dysfunction: A New Mechanism of Pregnancy Loss Associated with Anti-Phospholipid Antibodies?

by
Zengshu Huang
1,2,†,
Zhijing Tang
1,2,†,
Haiyun Guan
1,2,
Wingting Leung
1,2,
Lu Wang
1,2,
Hexia Xia
1,2 and
Wei Zhang
1,2,*
1
Obstetrics and Gynecology Hospital, Fudan University, Shanghai 200011, China
2
Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Shanghai 200011, China
*
Author to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Biomedicines 2022, 10(12), 3296; https://doi.org/10.3390/biomedicines10123296
Submission received: 22 November 2022 / Revised: 11 December 2022 / Accepted: 15 December 2022 / Published: 19 December 2022
(This article belongs to the Special Issue 10th Anniversary of Biomedicines-Immunopathogenesis of Autoimmune Diseases)
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Abstract

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.
Keywords: antiphospholipid antibody; trophoblast; Yes-associated protein; cell biological function; progesterone antiphospholipid antibody; trophoblast; Yes-associated protein; cell biological function; progesterone

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MDPI and ACS Style

Huang, Z.; Tang, Z.; Guan, H.; Leung, W.; Wang, L.; Xia, H.; Zhang, W. Inactivation of Yes-Associated Protein Mediates Trophoblast Dysfunction: A New Mechanism of Pregnancy Loss Associated with Anti-Phospholipid Antibodies? Biomedicines 2022, 10, 3296. https://doi.org/10.3390/biomedicines10123296

AMA Style

Huang Z, Tang Z, Guan H, Leung W, Wang L, Xia H, Zhang W. Inactivation of Yes-Associated Protein Mediates Trophoblast Dysfunction: A New Mechanism of Pregnancy Loss Associated with Anti-Phospholipid Antibodies? Biomedicines. 2022; 10(12):3296. https://doi.org/10.3390/biomedicines10123296

Chicago/Turabian Style

Huang, Zengshu, Zhijing Tang, Haiyun Guan, Wingting Leung, Lu Wang, Hexia Xia, and Wei Zhang. 2022. "Inactivation of Yes-Associated Protein Mediates Trophoblast Dysfunction: A New Mechanism of Pregnancy Loss Associated with Anti-Phospholipid Antibodies?" Biomedicines 10, no. 12: 3296. https://doi.org/10.3390/biomedicines10123296

APA Style

Huang, Z., Tang, Z., Guan, H., Leung, W., Wang, L., Xia, H., & Zhang, W. (2022). Inactivation of Yes-Associated Protein Mediates Trophoblast Dysfunction: A New Mechanism of Pregnancy Loss Associated with Anti-Phospholipid Antibodies? Biomedicines, 10(12), 3296. https://doi.org/10.3390/biomedicines10123296

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