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.