The regulation of mesangial cell proliferation

Mesangial cell (MC) proliferation is a key pathological feature in a number of common human renal diseases including IgA, systemic lupus erythematosus and diabetic nephropathies. Knowledge of the role of MCs in normal glomeruli and of their response to pathological stimuli is crucial to the understanding of these disease processes. The purpose of understanding disease is ultimately to develop therapeutic strategies that can limit or even reverse the underlying pathological process. Over the last 20 years a number of signaling pathways involved in the regulation of MC proliferation have been identified and studied with a view to manipulating them for therapeutic gain. Unfortunately, despite these advances, there are still very few clinical options that specifically target aberrant MC proliferation. This article reviews a number of factors that have been shown to play a role in controlling MC proliferation, including signaling molecules (e.g. Platelet-derived growth factor, Ras and Ca(2+)), cell cycle proteins (e.g. cyclin D1) and transcription factors (E2F). A variety of strategies has been used to manipulate these different pathways to elucidate their function in MCs with the ultimate aim of modifying them in order to treat human renal diseases.