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Functional activity of epidermal growth factor receptors in autosomal recessive polycystic kidney disease. Am J Physiol 1998 Sep;275(3):F387-94

Date

09/08/1998

Pubmed ID

9729511

DOI

10.1152/ajprenal.1998.275.3.F387

Scopus ID

2-s2.0-0344527449 (requires institutional sign-in at Scopus site)   92 Citations

Abstract

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.

Author List

Sweeney WE Jr, Avner ED

Author

Ellis D. Avner MD Professor in the Pediatrics department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Animals
Bromodeoxyuridine
DNA
Disease Models, Animal
Epidermal Growth Factor
ErbB Receptors
Humans
Immunohistochemistry
Immunosorbent Techniques
Mice
Mice, Inbred BALB C
Mice, Inbred C3H
Mice, Inbred C57BL
Phosphorylation
Polycystic Kidney, Autosomal Recessive