Chagas disease is considered important and presents intense inflammatory and fibrotic processes induced by the perpetuation of the parasite in the affected tissues and organs. Therefore, it is necessary to inquire about the host defense and attack mechanisms to have a more detailed knowledge about Chagas disease. MicroRNAs are found in blood, tissues and extracellular vesicles. These small regulators of gene expression are involved in physiological and pathological processes in both mammals and parasites. Several microRNAs have deregulated expression in chagasic heart disease, although little is known about their extracellular expression. Our main objective was to evaluate the involvement of miR-21, miR-146a and miR-155 in several samples from mice infected with the TcI Ninoa strain from the acute and indeterminate phases. We also explored a potential functional association of the selected microRNAs using STRING software. This software identified 23 pathways associated with Trypanosoma cruzi infection. In addition, eleven genes were identified through bioinformatics analysis, and we found that SMAD family member 5 was downregulated in both phases. This gene serves as a mediator in the TGF-β signaling pathway. Thus, forty female mice of the CD1 strain were distributed into 4 groups and the expression levels of miR-21, miR-146a and miR-155 were measured in samples of heart tissue, total plasma and plasma extracellular vesicles by quantitative real-time polymerase chain reaction. Overexpression of miR-21, miR-146a and miR-155 was observed in heart and plasma in both phases. Moreover, in extracellular vesicles miR-21 and miR-146a were also overexpressed in the acute phase, whereas in the indeterminate chronic phase we found only miR-146a up-regulated. The expression of inflammatory microRNAs miR-21, miR-146a and miR-155 were up-regulated in each of the samples from acutely and chronically infected mice. The relevant finding was that miR-146a was up-regulated in each sample in both phases; therefore, this miRNA could be a possible candidate biomarker in Chagas disease.

中文翻译：

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循环 miR-146a 作为南美锥虫病不确定阶段可能的候选生物标志物

恰加斯病被认为是重要的，并且表现出由寄生虫在受影响的组织和器官中持续存在引起的强烈炎症和纤维化过程。因此，有必要了解宿主的防御和攻击机制，以更详细地了解恰加斯病。MicroRNA 存在于血液、组织和细胞外囊泡中。这些基因表达的小调节因子参与了哺乳动物和寄生虫的生理和病理过程。几种 microRNA 在 chagasic 心脏病中的表达失调，尽管对其细胞外表达知之甚少。我们的主要目标是评估 miR-21、miR-146a 和 miR-155 在来自感染急性和不确定期 TcI Ninoa 菌株的小鼠的几个样本中的参与情况。我们还使用 STRING 软件探索了所选 microRNA 的潜在功能关联。该软件确定了与克氏锥虫感染相关的 23 条通路。此外，通过生物信息学分析鉴定了 11 个基因，我们发现 SMAD 家族成员 5 在两个阶段都被下调。该基因在 TGF-β 信号通路中充当介质。因此，将 40 只 CD1 株雌性小鼠分为 4 组，并通过定量实时聚合酶测量心脏组织、总血浆和血浆细胞外囊泡样本中 miR-21、miR-146a 和 miR-155 的表达水平。连锁反应。在两个阶段的心脏和血浆中均观察到 miR-21、miR-146a 和 miR-155 的过表达。而且，在细胞外囊泡中，miR-21 和 miR-146a 在急性期也过表达，而在不确定的慢性期，我们发现只有 miR-146a 上调。炎性微RNA miR-21、miR-146a和miR-155的表达在来自急性和慢性感染小鼠的每个样品中上调。相关发现是 miR-146a 在两个阶段的每个样品中均上调；因此，该 miRNA 可能是南美锥虫病的候选生物标志物。