HtrA4 is up-regulated during trophoblast syncytialization and BeWo cells fail to syncytialize without HtrA4

Abstract The outer layer of the human placenta comprises syncytiotrophoblast, which forms through fusion of cytotrophoblasts (syncytialization), and plays a critical role in maternal–fetal communication including nutrient/oxygen transportation and hormone secretion. Impairment in syncytialization in...

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Autores principales:	Mary Mansilla, Yao Wang, Rebecca Lim, Kirsten Palmer, Guiying Nie
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/1a9decc5b1fb47a3bf3e470a054c69aa
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spelling	oai:doaj.org-article:1a9decc5b1fb47a3bf3e470a054c69aa2021-12-02T16:14:09ZHtrA4 is up-regulated during trophoblast syncytialization and BeWo cells fail to syncytialize without HtrA410.1038/s41598-021-93520-12045-2322https://doaj.org/article/1a9decc5b1fb47a3bf3e470a054c69aa2021-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-93520-1https://doaj.org/toc/2045-2322Abstract The outer layer of the human placenta comprises syncytiotrophoblast, which forms through fusion of cytotrophoblasts (syncytialization), and plays a critical role in maternal–fetal communication including nutrient/oxygen transportation and hormone secretion. Impairment in syncytialization inevitably affects pregnancy outcomes. High temperature requirement factor A 4 (HtrA4) is a placental-specific protease, expressed by various trophoblasts including syncytiotrophoblast, and significantly elevated in preeclampsia at disease presentation. However, it is unknown whether HtrA4 is important for syncytialization. Here we first examined HtrA4 expression in primary human cytotrophoblasts during syncytialization which occurs spontaneously in culture, and in BeWo cells which syncytialize upon forskolin stimulation. The success of syncytialization in each model was confirmed by significant up-regulation/secretion of β-hCG, and the concurrent down-regulation of E-cadherin. In both models, HtrA4 mRNA and protein increased concomitantly with syncytialization. Furthermore, the secreted levels of β-hCG and HtrA4 correlated significantly and positively in both models. We next knocked out HtrA4 in BeWo by CRISPR/Cas9. Upon forskolin treatment, control BeWo profoundly up-regulated β-hCG and syncytin-1, down-regulated E-cadherin, and at the same time increased the formation of multinucleated cells, whereas BeWo cells without HtrA4 did not alter any of these parameters. Our data thus suggest that HtrA4 plays an essential role in syncytialization.Mary MansillaYao WangRebecca LimKirsten PalmerGuiying NieNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-14 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Mary Mansilla Yao Wang Rebecca Lim Kirsten Palmer Guiying Nie HtrA4 is up-regulated during trophoblast syncytialization and BeWo cells fail to syncytialize without HtrA4
description	Abstract The outer layer of the human placenta comprises syncytiotrophoblast, which forms through fusion of cytotrophoblasts (syncytialization), and plays a critical role in maternal–fetal communication including nutrient/oxygen transportation and hormone secretion. Impairment in syncytialization inevitably affects pregnancy outcomes. High temperature requirement factor A 4 (HtrA4) is a placental-specific protease, expressed by various trophoblasts including syncytiotrophoblast, and significantly elevated in preeclampsia at disease presentation. However, it is unknown whether HtrA4 is important for syncytialization. Here we first examined HtrA4 expression in primary human cytotrophoblasts during syncytialization which occurs spontaneously in culture, and in BeWo cells which syncytialize upon forskolin stimulation. The success of syncytialization in each model was confirmed by significant up-regulation/secretion of β-hCG, and the concurrent down-regulation of E-cadherin. In both models, HtrA4 mRNA and protein increased concomitantly with syncytialization. Furthermore, the secreted levels of β-hCG and HtrA4 correlated significantly and positively in both models. We next knocked out HtrA4 in BeWo by CRISPR/Cas9. Upon forskolin treatment, control BeWo profoundly up-regulated β-hCG and syncytin-1, down-regulated E-cadherin, and at the same time increased the formation of multinucleated cells, whereas BeWo cells without HtrA4 did not alter any of these parameters. Our data thus suggest that HtrA4 plays an essential role in syncytialization.
format	article
author	Mary Mansilla Yao Wang Rebecca Lim Kirsten Palmer Guiying Nie
author_facet	Mary Mansilla Yao Wang Rebecca Lim Kirsten Palmer Guiying Nie
author_sort	Mary Mansilla
title	HtrA4 is up-regulated during trophoblast syncytialization and BeWo cells fail to syncytialize without HtrA4
title_short	HtrA4 is up-regulated during trophoblast syncytialization and BeWo cells fail to syncytialize without HtrA4
title_full	HtrA4 is up-regulated during trophoblast syncytialization and BeWo cells fail to syncytialize without HtrA4
title_fullStr	HtrA4 is up-regulated during trophoblast syncytialization and BeWo cells fail to syncytialize without HtrA4
title_full_unstemmed	HtrA4 is up-regulated during trophoblast syncytialization and BeWo cells fail to syncytialize without HtrA4
title_sort	htra4 is up-regulated during trophoblast syncytialization and bewo cells fail to syncytialize without htra4
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/1a9decc5b1fb47a3bf3e470a054c69aa
work_keys_str_mv	AT marymansilla htra4isupregulatedduringtrophoblastsyncytializationandbewocellsfailtosyncytializewithouthtra4 AT yaowang htra4isupregulatedduringtrophoblastsyncytializationandbewocellsfailtosyncytializewithouthtra4 AT rebeccalim htra4isupregulatedduringtrophoblastsyncytializationandbewocellsfailtosyncytializewithouthtra4 AT kirstenpalmer htra4isupregulatedduringtrophoblastsyncytializationandbewocellsfailtosyncytializewithouthtra4 AT guiyingnie htra4isupregulatedduringtrophoblastsyncytializationandbewocellsfailtosyncytializewithouthtra4
_version_	1718384337521475584

HtrA4 is up-regulated during trophoblast syncytialization and BeWo cells fail to syncytialize without HtrA4

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