Cellular consequences of mesangial IgA deposition in IgA nephropathy

• Grant number: 10/51813-3
• Support Opportunities: Regular Research Grants
• Start date: April 01, 2011
• End date: May 31, 2013
• Field of knowledge: Health Sciences - Medicine
• Agreement: INSERM
• Principal Investigator: Niels Olsen Saraiva Câmara
• Grantee: Niels Olsen Saraiva Câmara
• Principal researcher abroad: Ivan Cruz Moura
• Institution abroad: Institut National de la Santé et de la Recherche Médicale (Inserm), France
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

IgA Nephropathy (IgAN), the major primary glomerulonephritis (GN) worldwide, is characterized by the mesangial deposition of IgA1-containing complexes (Monteiro et al., 2002). This apparently benign condition was revealed to be a major health problem due to the fact that around 25 to 40% of patients progress to end-stage renal disease following 20 years of disease onset (Coppo and D'Amico, 2005). We have previously identified and characterized the Transferrin receptor 1 (TfR1/CD71) as the mesangial IgA1 receptor (Moura et al., 2001). We showed that IgA1 glycosylation and size (both altered in IgAN patients) are essential for binding to TfR1 (Moura et al., 2004). We also demonstrated that in vitro stimulation of human mesangial cells (HMC) by IgA1 induces TfR1 expression, which initiates a positive feedback loop that allows an increased mesangial IgA1 deposition and cell activation (Moura et al., 2005). Recently, we aimed to characterize the signaling pathways implicated in mesangial cell response to patients' IgA1-complexes. This project aims to better characterize the cellular consequences of mesangial IgA deposition and its implication in IgAN pathogenesis. The two groups involved in this proposal have started a collaboration three years ago aiming to transfer technology and expertise in glomerular diseases and their consequences in the biology mesangial cells and the neighboring kidney cells. Large scale studies in patients' biopsies were started in order to validate data observed in vitro and in animal models. Altogether our results open new perspectives in the understanding of GN pathology and provides new therapeutic alternatives these diseases. (AU)