Study of the glycolytic function of the developmental factor HIF-1a and long noncoding RNA HIF1A-AS3 in the metabolism of macrophages infected with L. infantum

• Grant number: 22/08700-0
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: August 01, 2023
• Status: Discontinued
• Field of knowledge: Biological Sciences - Parasitology
• Principal Investigator: Sandra Marcia Muxel
• Grantee: Jonathan Miguel Zanatta
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated scholarship(s): 24/06233-1 - Role of long noncoding RNA HIF1A-AS3 in immunometabolism of murine macrophage infection with Leishmania infantum, BE.EP.DR

Abstract

In this project, we aim to evaluate the interaction of the Hypoxia inducible-factor 1a transcription factor (HIF-1a) and the long noncoding RNA HIF1A-AS3 and its role in glycolytic metabolism in macrophages infected with Leishmania infantum. We hypothesized that infection with L. infantum changes the oxygen supply and induces the gene expression of HIF-1± and the lncRNA encoded in the antisense strand of HIF1 sequence (HIF1A-AS3). The interaction between HIF1A-AS3 and the HIF-1a and its target genes would turn macrophage activation and immunometabolism, increasing susceptibility to infection. The lncRNAs expression has been altered in Leishmania-infected macrophages and can mediate the activation of the pro-inflammatory response or subversion of the host response. The interaction between HIF-1± and HIF1A-AS3 sets up an activation complex with other factors that lead to increased transcriptional levels of hexokinase II and lactate dehydrogenase genes and glycolysis in tumors cells agents, influencing tumor growth. Understanding the modulation of macrophage activation mediated by HIF-1a and HIF1A-AS3, its influence on the transcriptional regulation of genes of the glycolytic pathway, and the survival or death of the parasite will be highly relevant to understanding how parasite and host factors contribute to the pathogenesis of leishmaniasis.