Ex vivo infection of human placental explants by trypanosoma cruzi reveals a microRNA profiles Similar to that seen in trophoblast differentiation
Author
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Medina, Lisvaneth
Author
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Guerrero Muñoz, Jesús Alejandro
Author
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Liempi Manquel, Ana Isabel
Author
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Castillo Rivas, Christian
Author
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Ortega, Yessica
Author
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Sepúlveda, Alfredo
Author
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Salomó Martínez, Fernando
Author
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Maya Arango, Juan Diego
Author
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Kemmerling Weis, Ulrike
Admission date
dc.date.accessioned
2022-07-13T19:16:54Z
Available date
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2022-07-13T19:16:54Z
Publication date
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2022
Cita de ítem
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Pathogens 2022, 11, 361
es_ES
Identifier
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10.3390/pathogens11030361
Identifier
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https://repositorio.uchile.cl/handle/2250/186692
Abstract
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Congenital Chagas disease, caused by the protozoan parasite Trypanosoma cruzi, is responsible for 22.5% of new cases each year. However, placental transmission occurs in only 5% of infected mothers and it has been proposed that the epithelial turnover of the trophoblast can be considered a local placental defense against the parasite. Thus, Trypanosoma cruzi induces cellular proliferation, differentiation, and apoptotic cell death in the trophoblast, which are regulated, among other mechanisms, by small non-coding RNAs such as microRNAs. On the other hand, ex vivo infection of human placental explants induces a specific microRNA profile that includes microRNAs related to trophoblast differentiation such as miR-512-3p miR-515-5p, codified at the chromosome 19 microRNA cluster. Here we determined the expression validated target genes of miR-512-3p and miR-515-5p, specifically human glial cells missing 1 transcription factor and cellular FLICE-like inhibitory protein, as well as the expression of the main trophoblast differentiation marker human chorionic gonadotrophin during ex vivo infection of human placental explants, and examined how the inhibition or overexpression of both microRNAs affects parasite infection. We conclude that Trypanosoma cruzi-induced trophoblast epithelial turnover, particularly trophoblast differentiation, is at least partially mediated by placenta-specific miR-512-3p and miR-515-5p and that both miRNAs mediate placental susceptibility to ex vivo infection of human placental explants. Knowledge about the role of parasite-modulated microRNAs in the placenta might enable their use as biomarkers, as prognostic and therapeutic tools for congenital Chagas disease in the future.
es_ES
Patrocinador
dc.description.sponsorship
Network of the European Union, Latin America and the Caribbean Countries on Joint Innovation and Research Activities (ERANet-LAC) ERANet17/HLH-0142
Comision Nacional de Investigacion Cientifica y Tecnologica (CONICYT)
CONICYT FONDECYT 1190341
1170126
3180452
es_ES
Lenguage
dc.language.iso
en
es_ES
Publisher
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MDPI
es_ES
Type of license
dc.rights
Attribution-NonCommercial-NoDerivs 3.0 United States