Pathogenic mechanisms in the development and progression of IgA nephropathy

Abstract

Primary IgA nephropathy (IgAN) has been defined as an immune complex-mediated glomerulonephritis, characterized by the predominant mesangial IgA deposition. The detailed molecular pathogenesis of this distinct disease entity remains largely unknown. In the recent few years, the response to glomerular and tubulointerstitial cell injury in most forms of renal disease has been linked with changes in cell number (proliferation and apoptosis) and cell size (hyperptrophy) in in vitro studies and experimental animal models. The specific aims of this thesis were to investigate the pathogenic mechanisms involved in the development and progression of human IgAN in the context of two major cellular responses to injury including apoptosis and cell cycle regulation. The studies show that cell-type specific and differential modulation of apoptotic and cell cycle regulatory proteins in association with the various microenvironments of distinct cellular compartments of the kidney, likely play a significant role in progressive renal injury in human IgAN.