Ex Vivo Infection of Human Placental Explants by Trypanosoma cruzi Reveals a microRNA Profile Similar to That Seen in Trophoblast Differentiation

被引:8
作者
Medina, Lisvaneth [1 ]
Alejandro Guerrero-Munoz, Jesus [1 ]
Isabel Liempi, Ana [1 ]
Castillo, Christian [1 ,2 ]
Ortega, Yessica [3 ]
Sepulveda, Alfredo [1 ]
Salomo, Fernando [1 ]
Diego Maya, Juan [4 ]
Kemmerling, Ulrike [1 ]
机构
[1] Univ Chile, Fac Med, Inst Ciencias Biomed, Programa Anat & Biol Desarrollo, Santiago 8380453, Chile
[2] Univ Las Amer, Fac Med Vet & Agron, Santiago 7500975, Chile
[3] Univ Los Andes, Fac Ciencias, Lab Enzimol Parasitos, Merida 5105, Venezuela
[4] Univ Chile, Fac Med, Inst Ciencias Biomed, Programa Farmacol Mol & Clin, Santiago 8380453, Chile
关键词
Trypanosoma cruzi; miRNAs; placenta; trophoblast differentiation; EXPRESSION PROFILE; C19MC MICRORNAS; PREGNANCY; PROLIFERATION; TURNOVER; TISSUE;
D O I
10.3390/pathogens11030361
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
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.
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页数:14
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