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-...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2017-07-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-017-07017-x |
| _version_ | 1818840497600331776 |
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| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-19T04:11:08Z |
| format | Article |
| id | doaj.art-d86da9a98d17490480dbca830c152fcc |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-19T04:11:08Z |
| publishDate | 2017-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-d86da9a98d17490480dbca830c152fcc2022-12-21T20:36:24ZengNature PortfolioScientific Reports2045-23222017-07-01711910.1038/s41598-017-07017-xAggregated transthyretin is specifically packaged into placental nano-vesicles in preeclampsiaMancy Tong0Shi-bin Cheng1Qi Chen2Joana DeSousa3Peter R. Stone4Joanna L. James5Lawrence W. Chamley6Surendra Sharma7Department of Obstetrics and Gynaecology, The University of AucklandDepartment of Pediatrics, Women and Infants Hospital-Warren Alpert Medical School of Brown UniversityDepartment of Obstetrics and Gynaecology, The University of AucklandMaternal Fetal Medicine, Auckland City HospitalDepartment of Obstetrics and Gynaecology, The University of AucklandDepartment of Obstetrics and Gynaecology, The University of AucklandDepartment of Obstetrics and Gynaecology, The University of AucklandDepartment of Pediatrics, Women and Infants Hospital-Warren Alpert Medical School of Brown UniversityAbstract 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.https://doi.org/10.1038/s41598-017-07017-x |
| spellingShingle | 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 Scientific Reports |
| 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 |
| url | https://doi.org/10.1038/s41598-017-07017-x |
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