Mir-190b negatively contributes to the Trypanosoma cruzi- infected cell survival by repressing PTEN protein expression

Abstract

Chagas disease, which is caused by the intracellular protozoanTrypanosoma cruzi, is a serious health problem in Latin America. The heart is one of the major organs affected by this parasitic infection. The pathogenesis of tissue remodelling, particularly regarding cardiomyocyte behaviour after parasite infection, and the molecular mechanisms that occur immediately following parasite entry into host cells are not yet completely understood. Previous studies have reported that the establishment of parasitism is connected to the activation of the phosphatidylinositol-3 kinase (PI3K), which controls important steps in cellular metabolism by regulating the production of the second messenger phosphatidylinositol-3,4,5-trisphosphate. Particularly, the tumour suppressor PTEN is a negative regulator of PI3K signalling. However, mechanistic details of the modulatory activity of PTEN on Chagas disease have not been elucidated. To address this question, H9c2 cells were infected with T. cruzi Berenice 62 strain and the expression of a specific set of microRNAs (miRNAs) were investigated. Our cellular model demonstrated that miRNA-190b is correlated to the decrease of cellular viability rates by negatively modulating PTEN protein expression in T. cruzi-infected cells.

Modulation of miR-145-5p and miR-146b-5p levels is linked to reduced parasite load in H9C2 Trypanosoma cruzi infected cardiomyoblasts

“…Chronic chagasic cardiomyopathy is the most frequent and severe form of CD, being the main cause of morbidity by cardiovascular impairment in endemic areas 63 . Efforts have been made to understand the role of global alterations of microRNAs expression profiles in controlling CCC pathogenesis related pathways 33 , 34 and previous studies focused on specific microRNA profiles 32 , 64 . The cardiac tissue is an important site for T. cruzi persistence in the host during the chronic phase of infection 65 , therefore, in this study, firstly we propose the validation of an in vitro experimental model to investigate T. cruzi interactions with the host cell using the rat H9C2 cardiomyoblast cell line, which will spare the use of animals to obtain primary cardiomyocyte cultures and speed off the investigation of parasite–host interactions.…”

“…There are several other miRNAs involved in CD establishment and progression 31 – 35 , 37 , 64 . Nevertheless, we evaluated the modulation of two miRNAs based on their regulation in experimental acute CD in previous studies 34 , 93 , and the involvement of miR-145-5p in cardiomyopathies 82 , 83 , 86 , 94 – 96 and miR-146b-5p in inflammatory processes 97 , 98 that are known to be dysregulated in CD.…”

Circulating miR-146a as a possible candidate biomarker in the indeterminate phase of Chagas disease

“…Expressions of miRNAs in cardiac tissue from the acute phase, indeterminate asymptomatic phase, and CCC have been explored using murine models and human subjects with Chagas disease. Our selection of miRNAs: miR-21, miR-155 and miR-146a were made based on the literature review of dilated cardiomyopathy, inflammatory processes, fibrosis, myocarditis, hypertrophy, and heart failure, which are alterations that characterize CCC [ 18 – 20 , 26 , 36 – 38 ].…”

Predicting host dependency factors of pathogens in Drosophila melanogaster using machine learning

“…A high ranking predHDF is Phosphatase and TENsin homolog ( PTEN ) ( Table 1 ). Expression of PTEN was increased in Trypanosoma cruzi infected cells to about 300% higher levels compared to controls six hours after infection [66] . In addition, rat myoblast (H9c2 cells) transient transfected cells with rno-miR-190b inhibitor (miR-190b blocks PTEN translation) had increased rates of infection compared to non-transfected controls [66] .…”