Pharmacological effect of pinostrobin on CFTR‐mediated Cl‐ secretion and renal cyst development in in vitro model of polycystic kidney disease

Abstract

Cystic fibrosis transmembrane conductance regulator (CFTR) plays crucial role in renal cyst expansion via increase in fluid accumulation. Evidence suggests that inhibition of CFTR retard cyst development and enlargement in polycystic kidney disease (PKD). Here we investigated the pharmacological effect of pinostrobin, a bioactive natural flavonoid on CFTR‐mediated Cl‐ secretion and renal cyst expansion in in vitro model; human autosomal dominant polycystic kidney disease (ADPKD) cell line and Type I Mardin Darby Canine Kidney (MDCK) cells. Treatment with pinostrobin (10 and 50 µM) significantly reduces MDCK cyst formation and enlargement in concentration‐dependent manner. Pinostrobin reduces the number of renal cyst colonies corresponding with a decrease in cell proliferation and extracellular signal‐regulated kinases (ERK) signaling. Additionally, pinostrobin retarded cyst expansion via inhibition on CFTR‐mediated chloride secretion. The inhibitory effect of pinostrobin was not due to the decrease in cell viability and activity of Na+‐K+‐ATPase. Our findings define that pinostrobin might be the candidate for further study as the therapeutic agents for PKD treatment.