Artigo Acesso aberto Produção Nacional Revisado por pares

Integration of miRNA and gene expression profiles suggest a role for miRNAs in the pathobiological processes of acute Trypanosoma cruzi infection

2017; Nature Portfolio; Volume: 7; Issue: 1 Linguagem: Inglês

10.1038/s41598-017-18080-9

ISSN

2045-2322

Autores

Ludmila Rodrigues Pinto Ferreira, Frederico Moraes Ferreira, Laurie Laugier, Sandrine Cabantous, Isabela Cunha Navarro, Darlan da Silva Cândido, Vagner Oliveira Carvalho Rigaud, Juliana Monte Real, Glaucia Vilar Pereira, Isabela Resende Pereira, Leonardo Alexandre de Souza Ruivo, Ramendra Pati Pandey, Marilda Savóia Nascimento, Jorge Kalil, Joseli Lannes-Vieira, Helder I. Nakaya, Christophe Chevillard, Edécio Cunha‐Neto,

Tópico(s)

Viral Infections and Immunology Research

Resumo

Chagas disease, caused by the parasite Trypanosoma cruzi, is endemic in Latin America. Its acute phase is associated with high parasitism, myocarditis and profound myocardial gene expression changes. A chronic phase ensues where 30% develop severe heart lesions. Mouse models of T. cruzi infection have been used to study heart damage in Chagas disease. The aim of this study was to provide an interactome between miRNAs and their targetome in Chagas heart disease by integrating gene and microRNA expression profiling data from hearts of T. cruzi infected mice. Gene expression profiling revealed enrichment in biological processes and pathways associated with immune response and metabolism. Pathways, functional and upstream regulator analysis of the intersections between predicted targets of differentially expressed microRNAs and differentially expressed mRNAs revealed enrichment in biological processes and pathways such as IFNγ, TNFα, NF-kB signaling signatures, CTL-mediated apoptosis, mitochondrial dysfunction, and Nrf2-modulated antioxidative responses. We also observed enrichment in other key heart disease-related processes like myocarditis, fibrosis, hypertrophy and arrhythmia. Our correlation study suggests that miRNAs may be implicated in the pathophysiological processes taking place the hearts of acutely T. cruzi-infected mice.

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