Medina Lisvaneth, Guerrero-Muñoz Jesús Alejandro, Liempi Ana Isabel, Castillo Christian, Ortega Yessica, Sepúlveda Alfredo, Salomó Fernando, Maya Juan Diego, Kemmerling Ulrike
Programa de Anatomía y Biología del Desarrollo, Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile, Santiago 8380453, Chile.
Facultad de Medicina Veterinaria y Agronomía, Universidad de Las Américas, Santiago 7500975, Chile.
Pathogens. 2022 Mar 16;11(3):361. doi: 10.3390/pathogens11030361.
Congenital Chagas disease, caused by the protozoan parasite , 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, 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 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.
先天性恰加斯病由原生动物寄生虫引起，每年导致22.5%的新发病例。然而，胎盘传播仅发生在5%的受感染母亲中，有人提出滋养层上皮细胞更新可被视为胎盘对该寄生虫的局部防御。因此，[寄生虫名称未给出]在滋养层中诱导细胞增殖、分化和凋亡性细胞死亡，这些过程除其他机制外，还受微小RNA等小非编码RNA的调控。另一方面，人胎盘外植体的体外感染诱导了一种特定的微小RNA谱，其中包括与滋养层分化相关的微小RNA，如miR-512-3p、miR-515-5p，它们在19号染色体微小RNA簇上编码。在此，我们确定了miR-512-3p和miR-515-5p的表达验证靶基因，特别是人类神经胶质缺失1转录因子和细胞FLICE样抑制蛋白，以及人胎盘外植体体外感染期间主要滋养层分化标志物人绒毛膜促性腺激素的表达，并研究了这两种微小RNA的抑制或过表达如何影响寄生虫感染。我们得出结论，诱导的滋养层上皮细胞更新，特别是滋养层分化，至少部分由胎盘特异性miR-512-3p和miR-515-5p介导，并且这两种微小RNA介导了人胎盘外植体体外感染的胎盘易感性。关于寄生虫调节的微小RNA在胎盘中作用的知识可能使其在未来用作先天性恰加斯病的生物标志物、预后和治疗工具。
