Alteration of exosomes secreted from renal tubular epithelial cells exposed to high-concentration oxalate

Abstract

Oxalate (Ox) is a metabolic end product that is produced by the kidneys and is associated with several pathological conditions. The accumulation of oxalate in the body is one of the factors that lead to calcium oxalate kidney stones. To simulate the high-concentration Ox environment in vivo, we established an in vitro model of high Ox using renal tubular epithelial (HK-2) cells. Cell viability and proliferation were assessed to evaluate the effects of various concentrations (0, 0.25, 0.5, 1, 2, 4, 5, 8 and 10Mm) of Ox on HK-2 cells to select the optimum concentration and time to extract the exosomes. Treatment with 0, 1, or 2 mM Ox altered the morphology and secretion capacity of exosomes. As the concentration of Ox increased, peak and mean particle size decreased, but exosomes particle concentration, exosome RNA, and exosome protein increased. Size, distribution, and rate of secretion, as well as RNA and protein content, differed among extracellular vesicle subtypes. Furthermore, the three subtypes of exosomes delivered different signal factors in the microenvironment. We therefore speculated that three subtypes of exosomes may play differing roles in intercellular signal communication and the formation of CaOx kidney stones.