Effects of natural products on cystic activity in kidney cells.

Abstract

Polycystic Kidney Disease (PKD) is a pathology that targets kidney cells by forming calcium protuberances in their cilia. Polycystin-2, the ciliary transmembrane protein that induces cystogenesis, is necessary to transport calcium to the Golgi apparatus; however, the misfolding of this protein leads to its aggregation in the lumen. The use of collagen Type I as an extracellular matrix and forskolin, a molecule that opens ion channels in the membrane, to induce cyst growth shows the detrimental effects of excessive calcium storage on the epithelial cells. Through a series of in vitro and 3D tissue culture experiments, we sought to determine if natural products, in particular aminosterols and catechins, could reduce the size and quantity of cysts in a PKD cellular model. These molecules are known to prevent the toxicity caused by pore-forming toxins and aggregates of misfolded proteins implicit in a range of neurodegenerative diseases. We found that increasing concentrations of specific aminosterols and tea catechins reduced cyst diameters, therein suggesting a new therapeutic approach to target cyst formation and growth.