Advanced search
Start date
(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

iR-294 and miR-410 Negatively Regulate Tnfa, Arginine Transporter Cat1/2, and Nos2 mRNAs in Murine Macrophages Infected with Leishmania amazonensi

Full text
Acuna, Stephanie Maia [1] ; Zanatta, Jonathan Miguel [1] ; de Almeida Bento, Camilla [1] ; Floeter-Winter, Lucile Maria [1] ; Muxel, Sandra Marcia [1, 2]
Total Authors: 5
[1] Univ Sao Paulo, Dept Fisiol, Inst Biociencias, BR-05508090 Sao Paulo, SP - Brazil
[2] Univ Sao Paulo, Dept Imunol, Inst Ciencias Biomed, BR-05508020 Sao Paulo, SP - Brazil
Total Affiliations: 2
Document type: Journal article
Source: ON-CODING RN; v. 8, n. 1 FEB 2022.
Web of Science Citations: 0

MicroRNAs are small non-coding RNAs that regulate cellular processes by the post-transcriptional regulation of gene expression, including immune responses. The shift in the miRNA profiling of murine macrophages infected with Leishmania amazonensis can change inflammatory response and metabolism. L-arginine availability and its conversion into nitric oxide by nitric oxide synthase 2 (Nos2) or ornithine (a polyamine precursor) by arginase 1/2 regulate macrophage microbicidal activity. This work aimed to evaluate the function of miR-294, miR-301b, and miR-410 during early C57BL/6 bone marrow-derived macrophage infection with L. amazonensis. We observed an upregulation of miR-294 and miR-410 at 4 h of infection, but the levels of miR-301b were not modified. This profile was not observed in LPS-stimulated macrophages. We also observed decreased levels of those miRNAs target genes during infection, such as Cationic amino acid transporters 1 (Cat1/Slc7a1), Cat2/Slc7a22 and Nos2; genes were upregulated in LPS stimuli. The functional inhibition of miR-294 led to the upregulation of Cat2 and Tnfa and the dysregulation of Nos2, while miR-410 increased Cat1 levels. miR-294 inhibition reduced the number of amastigotes per infected macrophage, showing a reduction in the parasite growth inside the macrophage. These data identified miR-294 and miR-410 biomarkers for a potential regulator in the inflammatory profiles of microphages mediated by L. amazonensis infection. This research provides novel insights into immune dysfunction contributing to infection outcomes and suggests the use of the antagomiRs/inhibitors of miR-294 and miR-410 as new therapeutic strategies to modulate inflammation and to decrease parasitism. (AU)

FAPESP's process: 18/24693-9 - Integration of signaling mediated by transcription factors, long-noncoding RNAs and microRNAs during immune response agaisnt Leishmania amazonensis infection
Grantee:Sandra Marcia Muxel
Support Opportunities: Regular Research Grants
FAPESP's process: 19/07089-3 - Influence of L-arginine and polyamines metabolism for transcripts and microRNAs profile in murine macrophages infected with Leishmania amazonensis
Grantee:Jonathan Miguel Zanatta
Support Opportunities: Scholarships in Brazil - Master
FAPESP's process: 18/18499-5 - Characterization of homeobox gene Cux1 and its intronic microRNA miR-721 in murine macrophages infected with Leishmania amazonensis
Grantee:Camilla de Almeida Bento
Support Opportunities: Scholarships in Brazil - Scientific Initiation
FAPESP's process: 17/23519-2 - Analysis of role of miRNAs and transcription factors on the regulation of gene expression of Leishmania amazonensis infected murine macrophages
Grantee:Stephanie Maia Acuna
Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
FAPESP's process: 14/50717-1 - Biochemical, physiological and functional genomic studies of Leishmania-macrophage interaction
Grantee:Lucile Maria Floeter-Winter
Support Opportunities: Research Projects - Thematic Grants