The hypoxia-induced factor 1 alpha (HIF-1±) and the metabolic and phenotypic profile of podocytes in a cellular stress microenvironment

• Grant number: 22/11246-0
• Support Opportunities: Scholarships in Brazil - Program to Stimulate Scientific Vocations
• Start date: January 09, 2023
• End date: February 28, 2023
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Niels Olsen Saraiva Câmara
• Grantee: Giovanna Vitória Aragão de Almeida Santos
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

The hypoxic response in cells and tissues is mediated by hypoxia-inducible transcription factors (HIF), among them HIF-1± plays an integral role in metabolic changes through adaptations of oxygen availability. Podocytes are cells of the immune system, present in all tissues of the body. They are found to accumulate in ischemic/hypoxic tissues and worsen tissue damage by producing reactive oxygen species and other toxic mediators that interrupt cellular metabolism and upregulate a number of transcription factors, including HIF-1±. Thus, the aim of this study is to identify the role of HIF-1± and podocyte metabolism after hypoxia/reoxygenation stimulation and in response to inflammatory stimuli. Therefore, immortalized podocytes will be stimulated with 1 µg/mL of LPS + 10 ng/mL of IFN-³ followed or not by a hypoxia protocol, where the cells will be kept in an incubator with an environment of 0.3% O2 and 5% oxygen. CO2 for 24 hours. The parameters of cell viability, gene expression of HIF-1±, IL-10, IL-1² and TNF-± and PKM2 and the quantification of lactate will be evaluated. Our hypothesis is that HIF-1± modulates changes in podocyte metabolism during exposure to LPS+IFN. (AU)