Involvement of the MAPK signaling pathway and the Egr-1 transcription factor in glomerulosclerosis

• Grant number: 24/00266-5
• Support Opportunities: Scholarships in Brazil - Master
• Start date: August 01, 2024
• End date: July 31, 2025
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Maria Oliveira de Souza
• Grantee: Heitor Macedo Braz
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Among the various factors that contribute to the evolution of CKD, focal segmental glomerulosclerosis (FSGS) gains relevance, while the glomerular fibrotic lesion corroborates the loss of renal function. Studies demonstrate that the transcription factor Early Growth Response (Egr-1) and mitogen-activated protein kinases (MAPK) are associated with kidney diseases, including glomerulosclerosis. Since MAPK is responsible for activating the Egr-1 transcription, the project will study this interaction associated with FSGS, analyzing how these signaling pathways and transcription act in glomerular fibrosis. In vivo and in vitro models will be used for this study. In the in vivo study,Balb/c male mice aged 5 weeks will be treated with Adriamycin (10 mg/kg/single dose intravenous; Doxorubucin) for induction of glomerulosclerosis. After 5 weeks of treatment, renal function andMetabolic parameters of the animals will be evaluated by individual metabolic cages over a period of 24 h. After euthanasia, the kidneys will be removed and analyzed by periodic acid-Schiff staining (PAS), immunofluorescence, immunohistochemistry and immunoblotting. In the in vitro study, differentiated podocytes from mice will be treated with Adriamycin in dose and response time curve. The contribution of the Egr-1 factor in the induction of pro-fibrotic components. By t-test, statistical analysis will be done to compare two groups and one-way ANOVA and Tukey post test for comparison between three or more groups. Values of P < 0.05 will be considered statistically significant. The results will be presented as a mean value ± standard deviation.