cAMP Regulates Cell Proliferation and Cyst Formation in Autosomal Polycystic Kidney Disease Cells

Abstract

Abstract.: Both epithelial cell proliferation and fluid accumulation are responsible for cyst growth in autosomal dominant polycystic kidney disease (ADPKD). It was previously reported that the cystic fibrosis transmembrane conductance regulator (CFTR) is expressed in cysts from ADPKD patients and suggested that cAMP-stimulated Cl- and fluid secretion occurs through CFTR. The purpose of this study was to investigate the role of cell proliferation in cyst formation in ADPKD and to explore further the role of fluid secretion in cyst growth. Primary cultures both of ADPKD epithelial cells and a mixed population of normal renal epithelial cells isolated from the cortex (HRCE cells) were used. This study tested whether cAMP was involved both in stimulating cell proliferation and formation of cysts in vitro. 3 H-Thymidine incorporation assays showed that epidermal growth factor stimulated proliferation both in ADPKD cells and HRCE cells. In addition, cAMP stimulated DNA synthesis and cell proliferation in ADPKD, but not HRCE, cells. The effects of cAMP and epidermal growth factor on cell growth in ADPKD cells were additive. cAMP also stimulated cyst enlargement and fluid secretion in ADPKD cells. By contrast, cyst formation and enlargement from HRCE cells occurred without cAMP. Fluid secretion into the cyst lumen was blocked by diphenylamine carboxylic acid (DPC) and glibenclamide in ADPKD cells but blocked only by DPC in HRCE cells. This study showed that ADPKD cells have unique characteristics; cAMP stimulates fluid secretion and cell proliferation, indicating cAMP plays a very important role in cyst growth during the course of ADPKD.