Characterization of microvesicles and mesangial cells derived-exosomes stimulated by glucose and evaluation of their possible role in cell communication

Abstract

Exosomes are extracellular vesicles involved in intercellular communication under physiological and pathophysiological conditions, altering the function of target cells. Substances carried by these microstructures, whose content is determined by the secreting cell, confer this capacity. Stimuli and/or insults to the cells producing exosomes are capable to modify the amount and the cargo of secreted macrovesicles that in turn can alter the function of target cells. The macrovesicles and exosomes can constitute a pathway to disseminate factors with pathophysiological potential. Mesangial Cells (MC) have a relevant physiological role in the regulation of glomerular filtration, and their dysfunction may contribute to functional changes in the glomerulus contributing to typical glomerular sclerosis of Diabetic Nephropathy (DN). Thus, the objectives of this project include an in vitro analysis of the ability of MC in culture to secrete exosomes. Also to evaluate their content under standard physiological conditions and after stimulation with high glucose concentration concerning the presence of inflammatory and profibrotic molecules as well as the components of the renin angiotensin system, classically involved in the pathophysiology of DN. We also intend to assess whether high glucose stimulated MC derived-exosomes would be able to alter the function of normal target MC cells, and of distinct cell lineages such as podocytes, endothelial cells and tubular cells (in vitro) or alter renal function (in vivo) by injection (subcapsular) of these vesicles in the kidneys of healthy animals. (AU)