Biliary epithelial cells from mice with congenital polycystic kidney disease are hyperresponsive to epidermal growth factor.

Abstract

Epithelial hyperplasia is an early feature of the renal and biliary lesions in autosomal recessive polycystic kidney disease (ARPKD). To explore the cellular basis of this hyperplasia we isolated, cultured, and characterized biliary tract epithelium from common bile duct explants of mice with ARPKD (the BPK mouse) and controls. Primary cultures resulted in dense colonies of contact-inhibited epithelial cells with a homogenous growth pattern. Colony growth in serum-free basal medium (BM) of BPK-derived cells was not different from controls. Supplementation of BM with epidermal growth factor (EGF) induced a proliferative response in BPK-derived cells that was significantly increased over controls as assessed by [3H]thymidine uptake and expressed as percent change over growth in BM (BPK 239% and controls 131% of BM growth). In contrast, no differences between BPK- and control-derived cells were found with regard to the effects of BM supplementation with IGF-I, IGF-II, acidic fibroblast growth factor, keratinocyte growth factor, hepatocyte growth factor, or transforming growth factor-beta. Primary culture of biliary epithelium may provide a useful in vitro model for the study of the cellular pathophysiology of ARPKD. Our data demonstrate that increased epithelial sensitivity to EGF-like proteins may play a role in biliary epithelial proliferative changes which parallel renal tubular epithelial proliferation in ARPKD.