Aggregated transthyretin is specifically packaged into placental nano-vesicles in preeclampsia

Abstract In preeclampsia, the serum levels of transthyretin, a carrier protein for thyroxine, are elevated. Transthyretin isolated from preeclamptic serum is also aggregated and can induce preeclampsia-like symptoms in pregnant IL10−/− mice. Using western blotting, immunofluorescence, ELISA and qRT-...

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Autores principales:	Mancy Tong, Shi-bin Cheng, Qi Chen, Joana DeSousa, Peter R. Stone, Joanna L. James, Lawrence W. Chamley, Surendra Sharma
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/d86da9a98d17490480dbca830c152fcc
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spelling	oai:doaj.org-article:d86da9a98d17490480dbca830c152fcc2021-12-02T15:06:20ZAggregated transthyretin is specifically packaged into placental nano-vesicles in preeclampsia10.1038/s41598-017-07017-x2045-2322https://doaj.org/article/d86da9a98d17490480dbca830c152fcc2017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-07017-xhttps://doaj.org/toc/2045-2322Abstract In preeclampsia, the serum levels of transthyretin, a carrier protein for thyroxine, are elevated. Transthyretin isolated from preeclamptic serum is also aggregated and can induce preeclampsia-like symptoms in pregnant IL10−/− mice. Using western blotting, immunofluorescence, ELISA and qRT-PCR, we investigated the production of transthyretin by preeclamptic placentae and whether transthyretin is carried into the maternal circulation via placental extracellular vesicles. Both total and aggregated transthyretin were present in higher levels in preeclamptic placentae compared to normotensive placentae (p < 0.05, n = 7), however the levels of transythretin mRNA were not significantly different (n = 8). Preeclamptic placentae secreted similar levels of total transthyretin compared to normotensive placentae (2352 ± 2949 ng/mL vs. 3250 ± 1864 ng/mL, mean ± SD, p > 0.05, n = 8), however in preeclampsia, a significant proportion is vesicle-associated (~48% vs 0%). Increased levels of aggregated transthyretin were specifically associated to preeclamptic nano-vesicles (p < 0.02, n = 8). This study showed that the placenta actively produces transthyretin and in preeclampsia, a significant amount is extruded into the maternal circulation via placental exracellular vesicles. The increased aggregation of transthyretin in preeclampsia occurs at the post-transcriptional level and while preeclamptic nano-vesicles may be removing a toxic aggregated protein from the placenta, they may also be delivering aggregated transthyretin to specific maternal organs, contributing to the pathogenesis of preeclampsia.Mancy TongShi-bin ChengQi ChenJoana DeSousaPeter R. StoneJoanna L. JamesLawrence W. ChamleySurendra SharmaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-9 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Mancy Tong Shi-bin Cheng Qi Chen Joana DeSousa Peter R. Stone Joanna L. James Lawrence W. Chamley Surendra Sharma Aggregated transthyretin is specifically packaged into placental nano-vesicles in preeclampsia
description	Abstract In preeclampsia, the serum levels of transthyretin, a carrier protein for thyroxine, are elevated. Transthyretin isolated from preeclamptic serum is also aggregated and can induce preeclampsia-like symptoms in pregnant IL10−/− mice. Using western blotting, immunofluorescence, ELISA and qRT-PCR, we investigated the production of transthyretin by preeclamptic placentae and whether transthyretin is carried into the maternal circulation via placental extracellular vesicles. Both total and aggregated transthyretin were present in higher levels in preeclamptic placentae compared to normotensive placentae (p < 0.05, n = 7), however the levels of transythretin mRNA were not significantly different (n = 8). Preeclamptic placentae secreted similar levels of total transthyretin compared to normotensive placentae (2352 ± 2949 ng/mL vs. 3250 ± 1864 ng/mL, mean ± SD, p > 0.05, n = 8), however in preeclampsia, a significant proportion is vesicle-associated (~48% vs 0%). Increased levels of aggregated transthyretin were specifically associated to preeclamptic nano-vesicles (p < 0.02, n = 8). This study showed that the placenta actively produces transthyretin and in preeclampsia, a significant amount is extruded into the maternal circulation via placental exracellular vesicles. The increased aggregation of transthyretin in preeclampsia occurs at the post-transcriptional level and while preeclamptic nano-vesicles may be removing a toxic aggregated protein from the placenta, they may also be delivering aggregated transthyretin to specific maternal organs, contributing to the pathogenesis of preeclampsia.
format	article
author	Mancy Tong Shi-bin Cheng Qi Chen Joana DeSousa Peter R. Stone Joanna L. James Lawrence W. Chamley Surendra Sharma
author_facet	Mancy Tong Shi-bin Cheng Qi Chen Joana DeSousa Peter R. Stone Joanna L. James Lawrence W. Chamley Surendra Sharma
author_sort	Mancy Tong
title	Aggregated transthyretin is specifically packaged into placental nano-vesicles in preeclampsia
title_short	Aggregated transthyretin is specifically packaged into placental nano-vesicles in preeclampsia
title_full	Aggregated transthyretin is specifically packaged into placental nano-vesicles in preeclampsia
title_fullStr	Aggregated transthyretin is specifically packaged into placental nano-vesicles in preeclampsia
title_full_unstemmed	Aggregated transthyretin is specifically packaged into placental nano-vesicles in preeclampsia
title_sort	aggregated transthyretin is specifically packaged into placental nano-vesicles in preeclampsia
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/d86da9a98d17490480dbca830c152fcc
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Aggregated transthyretin is specifically packaged into placental nano-vesicles in preeclampsia

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