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Integration of signaling mediated by transcription factors, long-noncoding RNAs and microRNAs during immune response agaisnt Leishmania amazonensis infection

Grant number: 18/24693-9
Support Opportunities:Regular Research Grants
Duration: June 01, 2019 - September 30, 2021
Field of knowledge:Biological Sciences - Parasitology
Principal Investigator:Sandra Marcia Muxel
Grantee:Sandra Marcia Muxel
Host Institution: Instituto de Biociências (IB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Associated researchers:Juliana Ide Aoki ; Lucile Maria Floeter-Winter ; Ricardo Andrade Zampieri

Abstract

The control of gene expression is a complex network that could be mediated by three regulators: 1) transcription factors (TFs), via binding to regulatory DNA regions such as promoters or enhancers in the target gene that regulated mRNA transcription; 2) long noncoding RNA (lncRNA), via interaction with DNA, RNA or protein, regulating the chromosomal structure, transcription of mRNAs and microRNAs (miRNAs), their splicing and even acting in the translation of proteins; and 3) miRNAs, via complementation with the 3'UTR of the target mRNA, regulating translation or establishing the degradation of the target gene transcript. Some TFs and miRNAs have benn described in the modulation host response to Leishmania infection. Therefore, the analysis of the expression profile and regulation mediated by TFs (NF-kB, IRF1 and Cux1), lncRNAs and miRNAs from macrophages infected by Leishmania amazonensis, will allow the understanding of how complex is the modulation of host gene expression network in response to parasite. Leishmania infection is strongly influenced by host genetic background. On the other hand, the parasite is able to subvert the host defenses through L-arginine metabolism to produce polyamines, in addition to expression regulation of cytokines and chemokines, resulting in parasite survival and replication. The central objective of this project is to evaluate the expression of TFs, lncRNAs and microRNAs, and metabolites, in human macrophages (derived from the THP-1 line) and BALB/c and C57BL/6 mice macrophages infected by L. amazonensis and to elucidate the role of each regulator in the infection control or in the parasite resistance against the immune response of different hosts. These data will allow to identify potential genetic markers capable to determine the disease prognosis. This project has the potential to produce scientific articles and presentations in national and international conferences, besides serves as an instrument for the intellectual formation and training of students. (AU)

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Scientific publications (11)
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
SOUZA, MARINA DE ASSIS; RAMOS-SANCHEZ, EDUARDO MILTON; MUXEL, SANDRA MARCIA; LAGOS, DIMITRIS; REIS, LUIZA CAMPOS; PEREIRA, VALERIA REGO ALVES; BRITO, MARIA EDILEUZA FELINTO; ZAMPIERI, RICARDO ANDRADE; KAYE, PAUL MARTIN; FLOETER-WINTER, LUCILE MARIA; et al. miR-548d-3p Alters Parasite Growth and Inflammation in Leishmania (Viannia) braziliensis Infection. FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY, v. 11, . (18/23512-0, 14/14756-2, 19/25393-1, 18/14398-0, 18/24693-9)
ACUNA, STEPHANIE MAIA; FLOETER-WINTER, LUCILE MARIA; MUXEL, SANDRA MARCIA. MicroRNAs: Biological Regulators in Pathogen-Host Interactions. CELLS, v. 9, n. 1, . (17/23519-2, 18/23512-0, 18/24693-9)
ACUNA, STEPHANIE MAIA; ZANATTA, JONATHAN MIGUEL; DE ALMEIDA BENTO, CAMILLA; FLOETER-WINTER, LUCILE MARIA; MUXEL, SANDRA MARCIA. iR-294 and miR-410 Negatively Regulate Tnfa, Arginine Transporter Cat1/2, and Nos2 mRNAs in Murine Macrophages Infected with Leishmania amazonensi. ON-CODING RN, v. 8, n. 1, . (18/24693-9, 19/07089-3, 18/18499-5, 17/23519-2, 14/50717-1)
RAMOS-SANCHEZ, EDUARDO MILTON; REIS, LUIZA CAMPOS; SOUZA, MARINA DE ASSIS; MUXEL, SANDRA MARCIA; SANTOS, KAMILA REIS; LAGOS, DIMITRIS; PEREIRA, VALERIA REGO ALVES; DE BRITO, MARIA EDILEUZA FELINTO; KAYE, PAUL MARTIN; FLOETER-WINTER, LUCILE MARIA; et al. miR-548d-3p Is Up-Regulated in Human Visceral Leishmaniasis and Suppresses Parasite Growth in Macrophages. FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY, v. 12, p. 14-pg., . (19/25393-1, 14/14756-2, 18/14398-0, 18/24693-9, 18/23512-0)
ZANATTA, JONATHAN MIGUEL; ACUNA, STEPHANIE MAIA; ANGELO, YAN DE SOUZA; BENTO, CAMILLA DE ALMEIDA; PERON, JEAN PIERRE SCHATZMAN; STOLF, BEATRIZ SIMONSEN; MUXEL, SANDRA MARCIA. Putrescine supplementation shifts macrophage L-arginine metabolism related-genes reducing Leishmania amazonensis infection. PLoS One, v. 18, n. 3, p. 25-pg., . (17/23519-2, 22/00291-4, 18/24693-9, 18/18499-5, 19/07089-3)
AOKI, JULIANA IDE; MUXEL, SANDRA MARCIA; ZAMPIERI, RICARDO ANDRADE; MUELLER, KARL ERIK; NERLAND, AUDUN HELGE; FLOETER-WINTER, LUCILE MARIA. Differential immune response modulation in early Leishmania amazonensis infection of BALB/c and C57BL/6 macrophages based on transcriptome profiles (vol 9, 19841, 2019). SCIENTIFIC REPORTS, v. 10, n. 1, p. 1-pg., . (18/24693-9, 14/50717-1, 16/03273-6, 18/23512-0)
AOKI, JULIANA IDE; MUXEL, SANDRA MARCIA; LARANJEIRA-SILVA, MARIA FERNANDA; ZAMPIERI, RICARDO ANDRADE; MULLER, KARL ERIK; NERLAND, AUDUN HELGE; FLOETER-WINTER, LUCILE MARIA. Dual transcriptome analysis reveals differential gene expression modulation influenced by Leishmania arginase and host genetic background. MICROBIAL GENOMICS, v. 6, n. 9, p. 13-pg., . (14/50717-1, 16/03273-6, 17/23933-3, 18/24693-9, 18/23512-0)
MARCIA MUXEL, SANDRA; MAMANI-HUANCA, MARICRUZ; AOKI, JULIANA IDE; ZAMPIERI, RICARDO ANDRADE; FLOETER-WINTER, LUCILE MARIA; LOPEZ-GONZALVEZ, ANGELES; BARBAS, CORAL. Metabolomic Profile of BALB/c Macrophages Infected with Leishmania amazonensis: Deciphering L-Arginine Metabolism. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v. 20, n. 24, . (17/23519-2, 18/23512-0, 18/24693-9, 16/03273-6)
MAMANI-HUANCA, MARICRUZ; MUXEL, SANDRA MARCIA; ACUNA, STEPHANIE MAIA; FLOETER-WINTER, LUCILE MARIA; BARBAS, CORAL; LOPEZ-GONZALVEZ, ANGELES. Metabolomic Reprogramming of C57BL/6-Macrophages during Early Infection with L. amazonensis. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v. 22, n. 13, . (17/23519-2, 18/24693-9, 18/23512-0)
FERNANDES, JULIANE C. R.; GONCALVES, ANDRE N. A.; FLOETER-WINTER, LUCILE M.; NAKAYA, HELDER I.; MUXEL, SANDRA M.. Comparative transcriptomic analysis of long noncoding RNAs in Leishmania-infected human macrophages. FRONTIERS IN GENETICS, v. 13, p. 17-pg., . (17/21906-9, 19/13880-5, 18/24693-9)
FERNANDES, JULIANE C. R.; ACUNA, STEPHANIE M.; AOKI, JULIANA, I; FLOETER-WINTER, LUCILE M.; MUXEL, SANDRA M.. Long Non-Coding RNAs in the Regulation of Gene Expression: Physiology and Disease. NON-CODING RNA, v. 5, n. 1, p. 25-pg., . (17/23519-2, 14/50717-1, 16/03273-6, 16/19815-2, 18/24693-9, 17/21906-9)

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