Proteomic analysis of extracellular and transcriptomic matrix in glomerular development and Idiopathic Collapsing Glomerulopathy

Abstract

In order to expand the understanding of glomerular development, cellular components and signaling pathways in homeostatic conditions between normal adult and pediatric renal tissue, we propose to evaluate the glomerular transcriptomic profile, single cell transcriptomic profile of glomerular cell subtypes and decode the protein composition of the Glomerular Extracellular Matrix (GEM). In parallel, we will broaden the understanding of the pathogenesis of human Collapsing Glomerulopathy (CG) through comparative analyses of GEM proteomic profiles and glomerular cell profiles between normal human renal tissue, Collapsing glomerulopathy associated and not associated with high-risk genotype of APOL1 and segmental and focal glomerulosclerosis-NOS, followed by in vitro functional evaluations. We will evaluate the impact of Extracellular Matrix (ECM) changes in 2D and animal experimental models. We hope to identify differences and similarities between the composition of GEM between humans and experimental animals, which will allow to refine the validity of laboratory animal models for evaluation of human diseases. We also hope to determine the main components of ECM with impact on the phenotype and cellular signaling pathways and to understand more deeply the evolutionary molecular profile of human glomeruli since childhood. (AU)