| Author | Farani, Priscila Silva Grijó | |
| Author | Ferreira, Beatriz Iandra Silva | |
| Author | Gibaldi, Daniel | |
| Author | Lannes-Vieira, Joseli | |
| Author | Moreira, Otacilio Cruz | |
| Access date | 2022-06-23T17:54:00Z | |
| Available date | 2022-06-23T17:54:00Z | |
| Document date | 2022 | |
| Citation | FARANI, Priscila Silva Grijó Farani et al. Modulation of miR‑145‑5p and miR‑146b‑5p levels is linked to reduced parasite load in H9C2 Trypanosoma cruzi infected cardiomyoblasts. Scientifc Reports, v. 12, 1436, p. 1 - 15, 2022. | pt_BR |
| ISSN | 2045-2322 | pt_BR |
| URI | https://www.arca.fiocruz.br/handle/icict/53452 | |
| Language | eng | pt_BR |
| Publisher | Nature Portfolio | pt_BR |
| Rights | open access | |
| Subject in Portuguese | Trypanosoma cruzi | pt_BR |
| Subject in Portuguese | Modulação de miR‑145‑5p | pt_BR |
| Subject in Portuguese | Níveis de miR‑146b‑5p | pt_BR |
| Subject in Portuguese | Redução | pt_BR |
| Subject in Portuguese | Carga parasitária em H9C2 | pt_BR |
| Subject in Portuguese | Infecção | pt_BR |
| Subject in Portuguese | Trypanosoma cruzi | pt_BR |
| Subject in Portuguese | Cardiomioblastos | pt_BR |
| Title | Modulation of miR‑145‑5p and miR‑146b‑5p levels is linked to reduced parasite load in H9C2 Trypanosoma cruzi infected cardiomyoblasts | pt_BR |
| Type | Article | |
| DOI | 10.1038/s41598-022-05493-4 | |
| Abstract | In the heart tissue of acutely Trypanosoma cruzi-infected mice miR-145-5p and miR-146b-5p are,
respectively, downregulated and upregulated. Here, we used the H9C2 rat cardiomyoblast cell line
infected with the Colombian T. cruzi strain to investigate the parasite-host cell interplay, focusing
on the regulation of miR-145-5p and miR-146b-5p expression. Next, we explored the effects of
interventions with the trypanosomicidal drug Benznidazole (Bz) alone or combined with Pentoxifylline
(PTX), a methylxanthine derivative shown to modulate immunological and cardiac abnormalities
in a model of chronic chagasic cardiomyopathy, on parasite load and expression of miR-145-5p
and miR-146b-5p. The infection of H9C2 cells with trypomastigote forms allowed parasite cycle
with intracellular forms multiplication and trypomastigote release. After 48 and 144 h of infection,
upregulation of miR-145-5p (24 h: 2.38 ± 0.26; 48 h: 3.15 ± 0.9-fold change) and miR-146b-5b (24 h:
2.60 ± 0.46; 48 h: 2.97 ± 0.23-fold change) was detected. The peak of both miRNA levels paralleled
with release of trypomastigote forms. Addition of 3 μM and 10 μM of Bz 48 h after infection reduced
parasite load but did not interfere with miR-145-5p and miR-146b-5p levels. Addition of PTX did
not interfere with Bz-induced parasite control efficacy. Conversely, combined Bz + PTX treatment
decreased the levels of both microRNAs, resembling the expression levels detected in non-infected
H9C2 cells. Moreover, the use of miR-145-5p and miR-146b-5p mimic/inhibitor systems before
infection of H9C2 cells decreased parasite load, 72 h postinfection. When H9C2 cells were treated
with miR-145-5p and miR-146b-5p mimic/inhibitor 48 h after infection, all the used systems, except
the miR-146b-5p inhibitor, reduced parasite load. Altogether, our data indicate that these microRNAs
putatively control signaling pathways crucial for parasite–host cell interaction. Thus, miR-145-5p and
miR-146b-5p deserve to be further investigated as biomarkers of parasite control and tools to identify
therapeutic adjuvants to etiological treatment in Chagas disease. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Molecular e Endemias. Plataforma de PCR em tempo real RPT09A. Rio de Janeiro, RJ, Brasil / Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia das Interações.Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Molecular e Endemias. Plataforma de PCR em tempo real RPT09A. Rio de Janeiro, RJ, Brasil | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia das Interações.Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia das Interações.Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Molecular e Endemias. Plataforma de PCR em tempo real RPT09A. Rio de Janeiro, RJ, Brasil | pt_BR |
| Subject | Trypanosoma cruzi | pt_BR |
| Subject | Modulation of miR‑145‑5p | pt_BR |
| Subject | miR‑146b‑5p levels | pt_BR |
| Subject | Reduced parasite load in H9C2 | pt_BR |
| Subject | Infected cardiomyoblastos | pt_BR |
