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Aggregated transthyretin is specifically packaged into placental nano-vesicles in preeclampsia
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...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Nature Publishing Group UK
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5532246/ https://www.ncbi.nlm.nih.gov/pubmed/28751735 http://dx.doi.org/10.1038/s41598-017-07017-x |
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author | Tong, Mancy Cheng, Shi-bin Chen, Qi DeSousa, Joana Stone, Peter R. James, Joanna L. Chamley, Lawrence W. Sharma, Surendra |
author_facet | Tong, Mancy Cheng, Shi-bin Chen, Qi DeSousa, Joana Stone, Peter R. James, Joanna L. Chamley, Lawrence W. Sharma, Surendra |
author_sort | Tong, Mancy |
collection | PubMed |
description | 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 | Online Article Text |
id | pubmed-5532246 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-55322462017-08-02 Aggregated transthyretin is specifically packaged into placental nano-vesicles in preeclampsia Tong, Mancy Cheng, Shi-bin Chen, Qi DeSousa, Joana Stone, Peter R. James, Joanna L. Chamley, Lawrence W. Sharma, Surendra Sci Rep Article 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. Nature Publishing Group UK 2017-07-27 /pmc/articles/PMC5532246/ /pubmed/28751735 http://dx.doi.org/10.1038/s41598-017-07017-x Text en © The Author(s) 2017 Open Access This 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 license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license 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 license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Tong, Mancy Cheng, Shi-bin Chen, Qi DeSousa, Joana Stone, Peter R. James, Joanna L. Chamley, Lawrence W. Sharma, Surendra Aggregated transthyretin is specifically packaged into placental nano-vesicles in preeclampsia |
title | 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_short | Aggregated transthyretin is specifically packaged into placental nano-vesicles in preeclampsia |
title_sort | aggregated transthyretin is specifically packaged into placental nano-vesicles in preeclampsia |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5532246/ https://www.ncbi.nlm.nih.gov/pubmed/28751735 http://dx.doi.org/10.1038/s41598-017-07017-x |
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