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Am J Physiol Renal Physiol 275: F387-F394, 1998;
0363-6127/98 $5.00
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Vol. 275, Issue 3, F387-F394, September 1998

Functional activity of epidermal growth factor receptors in autosomal recessive polycystic kidney disease

William E. Sweeney Jr. and Ellis D. Avner

Department of Pediatrics, Rainbow Babies and Children's Hospital, and Case Western Reserve University, Cleveland, Ohio 44106-6003

Evidence from a number of laboratories suggests a potential role for the epidermal growth factor (EGF)-transforming growth factor-alpha -epidermal growth factor receptor (EGF-R) axis in promoting epithelial hyperplasia and cyst formation in autosomal recessive polycystic kidney disease (ARPKD). As previously reported, in the C57BL-6Jcpk/cpk (CPK), BALB/c-bpk/bpk (BPK), and C3H-orpk/orpk (ORPK) murine models of ARPKD, as well as in human ARPKD and human ADPKD, the EGF-R is mislocated to the apical surface of cystic collecting tubule (CT) epithelial cells. The present studies demonstrate that cells from cystic and control CTs can be isolated and that these cells maintain their in vivo EGF-R phenotype in vitro. Domain-specific high-affinity ligand binding was assessed by standard Scatchard analysis, and selective ligand stimulation of apical vs. basolateral EGF-R in these cells was followed by measurement of receptor autophosphorylation and determination of cell proliferation. These studies demonstrate that in vitro apically expressed EGF-Rs exhibit high-affinity binding for EGF, autophosphorylate in response to EGF, and transmit a mitogenic signal when stimulated by the appropriate ligand.

cyst formation; epithelial hyperplasia; receptor autophosphorylation


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