Role of matrix metalloproteinases in the development and progression of renal fibrosis.

• Grant number: 24/22770-7
• Support Opportunities: Regular Research Grants
• Start date: May 01, 2025
• End date: April 30, 2028
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Maria Oliveira de Souza
• Grantee: Maria Oliveira de Souza
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

The progression from acute kidney injury (AKI) to chronic kidney disease (CKD) is a reality for millions of people around the world. Even with the advancement of scientific investigations, there is still a lack of information about cell signaling pathways around this topic, especially relative to renal fibrosis. Some studies have highlighted the importance of matrix metalloproteinases (MMPs) in AKI and CKD progression, but the relationship between MMPs and fibrotic elements in renal pathologies are still unclear. Thus, our hypothesis is that in the progression of kidney injury there is the formation of a fibrogenic niche, with the participation of MMPs 2, 7, 9 and 10 regulating inflammatory responses and the progression of fibrosis in different phases of kidney injury. To answer this hypothesis, we present three objectives in the form of subprojects: 1) To investigate the contribution of MMPs 2, 7, 9 and 10, in addition to the proteins tenascin C and Sonic hedgehog (Shh) in renal fibrosis characterized by adriamycin induced-focal segmental glomerulosclerosis (FSGS); 2) To investigate the participation of MMP10 and fibrillin 1 in the renal fibrotic response in a model of unilateral nephrectomy associated with crystalline nephropathy, and 3) To evaluate the participation of MMPs 2, 7, 9, 10 and serpin A10 in the renal fibrotic response in a model of unilateral ischemia and reperfusion associated with unilateral nephrectomy. Our expectation is that the results obtained in this study may contribute significantly to the discovery and/or improvement of regulatory molecules of MMP activity expressed in the kidneys, as well as possible inhibitors of cellular pathways involved in the generation or progression of renal fibrosis. (AU)