Function of p38MAPK and p53 in modulating MMP10 in proximal tubule cells in model of glomerulosclerosis caused by adriamycin.

• Grant number: 25/01466-0
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: March 01, 2025
• End date: February 28, 2026
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Maria Oliveira de Souza
• Grantee: Eduarda Gomes Rodrigues
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

The progression of acute kidney injury (AKI) to chronic kidney disease (CKD) is a reality for millionsof people around the world. Despite the advances in scientific research, there is still a lack of information onthe cellular signaling pathways involved in this issue, especially in relation to renal fibrosis and tubular injury.Some studies have highlighted the importance of matrix metalloproteinase 10 (MMP10) in AKI and in theprogression of CKD, but the relationship between MMP10 and fibrotic elements, as well as the signalingpathways responsible for tubular injury in renal pathologies, is unclear. Thus, our hypothesis is that in theprogression of renal tubular injury induced by adriamycin, there is activation of p38MAPK and p53 withconsequent activation of MMP10, which results in apoptosis, formation of a fibrogenic niche and progressionof fibrosis in different phases of renal injury. To answer this hypothesis, the aim of this study is to investigatethe contribution of p38MAPK and p53 in the modulation of MMP10 in tubular injury induced by adriamycinin a model of focal segmental glomerulosclerosis (FSGS). The study will be performed in vivo models(control animals or treated with adriamycin 10 mg/kg) and in vitro (control TKPTS cells or treated withadriamycin 1¿M and/or SB203580, a p38MAPK inhibitor 1¿M). The expected methodologies include westernblotting, immunohistochemistry and immunofluorescence to evaluate protein expression and distribution.Statistical analysis will be performed using the one-way or two-way ANOVA method and the Bonferroni post-test and, when necessary, the t-test. p<0.05 will be considered significant in comparison to the control ortreated animals. The results will be presented as mean value ± standard deviation.We expect that the results obtained in this study may contribute significantly to the discovery and/orimprovement of molecules that regulate the activity of MMP10 expressed in the kidneys.