Contribution of HIF-1¿ to the production of extracellular vesicles by renal cells in an anoxia/reoxygenation model.

• Grant number: 25/25281-0
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: February 01, 2026
• End date: January 31, 2027
• Field of knowledge: Biological Sciences - Morphology - Cytology and Cell Biology
• Principal Investigator: Marcela Sorelli Carneiro Ramos
• Grantee: Isabella Rossoni Ribeiro
• Host Institution: Centro de Ciências Naturais e Humanas (CCNH). Universidade Federal do ABC (UFABC). Santo André , SP, Brazil
• Associated research grant: 24/02928-5 - Cardiac shifting from structural changes to electrical alterations during acute kidney injury to chronic kidney disease transition., AP.TEM

Abstract

Under low oxygen concentrations, a condition known as hypoxia, mammalian cells rely on mechanisms to ensure survival, among which the hypoxia-inducible factor (HIF) stands out. Its HIF-1¿ subunit, which regulates more than 100 genes, is particularly noteworthy. Activation of the HIF complex is related to an increase in the production of extracellular vesicles (EVs) and changes in their content. EVs are an important group of particles released by all cell types, promoting intercellular communication through the transport of biomolecules. These mechanisms are associated with numerous processes in the organism and play a fundamental role in maintaining renal physiology. Acute kidney injury (AKI) is defined as the sudden loss of kidney function, usually preceded by ischemia-reperfusion injury, and is associated with approximately 1.7 million deaths every year. Although there is evidence of the concomitant involvement of HIF-1¿ and EVs in the development of the lesion, there are few studies that directly associate these mechanisms. Thus, this project proposes to evaluate the contribution of HIF-1¿ in the production of extracellular vesicles by proximal renal tubular cells subjected to an AKI model by anoxia/reoxygenation. For this, proximal renal tubular cells (HK-2) will be subjected to anoxia and treated with an inhibitor of HIF-1¿ activity. The culture medium of the different experimental groups will be collected and the EVs will be extracted by size exclusion chromatography (SEC) and differential ultracentrifugation. They will be characterized by western blotting (antibodies specific to certain EVs) and nanoparticle tracking analysis (NTA). The statistical analysis will be conducted by one-way or two-way ANOVA, followed by Tukey's test, considering p<0.05 as significant. At the end of this study, we hope to understand whether HIF-1¿ contributes to the production of EVs in an oxygen-deprived scenario. (AU)