HEPATOCYTE GROWTH-FACTOR ALTERS THE POLARITY OF MADIN-DARBY CANINE KIDNEY-CELL MONOLAYERS

Hepatocyte growth factor (HGF) and E-cadherin are important for epithe lial morphogenetic events. We examined the effects of HGF on E-cadheri n localization and interaction with beta-catenin in polarized Madin-Da rby canine kidney (MDCK) cell monolayers grown on filters. Surface bio tinylation experiments showed that HGF increases apically accessible E -cadherin. Confocal immunofluorescence microscopy of HGF-treated cells showed localization of E-cadherin at membrane domains contacting the apical compartment and an increase in accessibility of apically applie d antibodies to lateral E-cadherin below the tight junction. Coimmunop recipitation of beta-catenin/E-cadherin complexes showed that the amou nt of E-cadherin associated with beta-catenin increased during the fir st 24 h of HGF treatment with a return to baseline values after 48 and 72 h. Metabolic labeling showed that HGF increased the synthetic rate of beta-catenin and the amount of newly synthesized E-cadherin associ ated with immunoprecipitated beta-catenin, with the peak effect occurr ing after 12 h of treatment and returning to baseline after 24 h. HGF treatment inhibited transcytosis of immunoglobulin A by the polymeric immunoglobulin receptor. We conclude that HGF treatment of polarized M DCK cells grown on filters decreases cell polarity and alters E-cadher in/beta-catenin interaction and synthesis.