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Abundance of megalin and Dab2 is reduced in syncytiotrophoblast during placental malaria, which may contribute to low birth weight

Placental malaria caused by Plasmodium falciparum contributes to ~200,000 child deaths annually, mainly due to low birth weight (LBW). Parasitized erythrocyte sequestration and consequent inflammation in the placenta are common attributes of placental malaria. The precise molecular details of placen...

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Autores principales: Lybbert, Jared, Gullingsrud, Justin, Chesnokov, Olga, Turyakira, Eleanor, Dhorda, Mehul, Guerin, Philippe J., Piola, Patrice, Muehlenbachs, Atis, Oleinikov, Andrew V.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4829923/
https://www.ncbi.nlm.nih.gov/pubmed/27072056
http://dx.doi.org/10.1038/srep24508
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author Lybbert, Jared
Gullingsrud, Justin
Chesnokov, Olga
Turyakira, Eleanor
Dhorda, Mehul
Guerin, Philippe J.
Piola, Patrice
Muehlenbachs, Atis
Oleinikov, Andrew V.
author_facet Lybbert, Jared
Gullingsrud, Justin
Chesnokov, Olga
Turyakira, Eleanor
Dhorda, Mehul
Guerin, Philippe J.
Piola, Patrice
Muehlenbachs, Atis
Oleinikov, Andrew V.
author_sort Lybbert, Jared
collection PubMed
description Placental malaria caused by Plasmodium falciparum contributes to ~200,000 child deaths annually, mainly due to low birth weight (LBW). Parasitized erythrocyte sequestration and consequent inflammation in the placenta are common attributes of placental malaria. The precise molecular details of placental changes leading to LBW are still poorly understood. We hypothesized that placental malaria may disturb maternofetal exchange of vitamins, lipids, and hormones mediated by the multi-ligand (n ~ 50) scavenging/signaling receptor megalin, which is abundantly expressed in placenta but was not previously analyzed in pregnancy outcomes. We studied abundance of megalin and its intracellular adaptor protein Dab2 by immunofluorescence microscopy in placental biopsies from Ugandan women with (n = 8) and without (n = 20) active placental malaria. We found that: (a) abundances of both megalin (p = 0.01) and Dab2 (p = 0.006) were significantly reduced in brush border of syncytiotrophoblast of infected placentas; (b) amounts of megalin and Dab2 were strongly correlated (Spearman’s r = 0.53, p = 0.003); (c) abundances of megalin and Dab2 (p = 0.046) were reduced in infected placentas from women with LBW deliveries. This study provides first evidence that placental malaria infection is associated with reduced abundance of megalin transport/signaling system and indicate that these changes may contribute to the pathology of LBW.
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spelling pubmed-48299232016-04-19 Abundance of megalin and Dab2 is reduced in syncytiotrophoblast during placental malaria, which may contribute to low birth weight Lybbert, Jared Gullingsrud, Justin Chesnokov, Olga Turyakira, Eleanor Dhorda, Mehul Guerin, Philippe J. Piola, Patrice Muehlenbachs, Atis Oleinikov, Andrew V. Sci Rep Article Placental malaria caused by Plasmodium falciparum contributes to ~200,000 child deaths annually, mainly due to low birth weight (LBW). Parasitized erythrocyte sequestration and consequent inflammation in the placenta are common attributes of placental malaria. The precise molecular details of placental changes leading to LBW are still poorly understood. We hypothesized that placental malaria may disturb maternofetal exchange of vitamins, lipids, and hormones mediated by the multi-ligand (n ~ 50) scavenging/signaling receptor megalin, which is abundantly expressed in placenta but was not previously analyzed in pregnancy outcomes. We studied abundance of megalin and its intracellular adaptor protein Dab2 by immunofluorescence microscopy in placental biopsies from Ugandan women with (n = 8) and without (n = 20) active placental malaria. We found that: (a) abundances of both megalin (p = 0.01) and Dab2 (p = 0.006) were significantly reduced in brush border of syncytiotrophoblast of infected placentas; (b) amounts of megalin and Dab2 were strongly correlated (Spearman’s r = 0.53, p = 0.003); (c) abundances of megalin and Dab2 (p = 0.046) were reduced in infected placentas from women with LBW deliveries. This study provides first evidence that placental malaria infection is associated with reduced abundance of megalin transport/signaling system and indicate that these changes may contribute to the pathology of LBW. Nature Publishing Group 2016-04-13 /pmc/articles/PMC4829923/ /pubmed/27072056 http://dx.doi.org/10.1038/srep24508 Text en Copyright © 2016, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Lybbert, Jared
Gullingsrud, Justin
Chesnokov, Olga
Turyakira, Eleanor
Dhorda, Mehul
Guerin, Philippe J.
Piola, Patrice
Muehlenbachs, Atis
Oleinikov, Andrew V.
Abundance of megalin and Dab2 is reduced in syncytiotrophoblast during placental malaria, which may contribute to low birth weight
title Abundance of megalin and Dab2 is reduced in syncytiotrophoblast during placental malaria, which may contribute to low birth weight
title_full Abundance of megalin and Dab2 is reduced in syncytiotrophoblast during placental malaria, which may contribute to low birth weight
title_fullStr Abundance of megalin and Dab2 is reduced in syncytiotrophoblast during placental malaria, which may contribute to low birth weight
title_full_unstemmed Abundance of megalin and Dab2 is reduced in syncytiotrophoblast during placental malaria, which may contribute to low birth weight
title_short Abundance of megalin and Dab2 is reduced in syncytiotrophoblast during placental malaria, which may contribute to low birth weight
title_sort abundance of megalin and dab2 is reduced in syncytiotrophoblast during placental malaria, which may contribute to low birth weight
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4829923/
https://www.ncbi.nlm.nih.gov/pubmed/27072056
http://dx.doi.org/10.1038/srep24508
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