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From the Department of Ophthalmology, and Department of Cell Biology, Neurobiology & Anatomy, Medical College of Wisconsin, Milwaukee.
PURPOSE. To determine whether retinal pigment epithelial (RPE) cells, which reportedly express N-cadherin as their major cadherin cell adhesion protein, also express the more common epithelial cadherin, E-cadherin.
METHODS. Cadherins expressed by human RPE cells in situ were examined by western blot analysis of extracts prepared from the RPE of human adult eyes. Cadherins expressed in vitro were examined by analysis of confluent and postconfluent human RPE cultures, using the methods of reverse transcriptionpolymerase chain reaction (RTPCR) and western blot analysis. Protein distribution was examined by conventional fluorescence microscopy, confocal imaging, or both. Proteins whose expression, distribution, or both correlated with E-cadherin expression in other epithelial cells were examined by similar methods in cultured RPE cells.
RESULTS. In addition to N-cadherin, E-cadherin (and P-cadherin) was found in
adult human RPE in situ. In cultured human RPE cells, N-cadherin was
ubiquitous, but E-cadherin was limited to patches of cells and was not
expressed until several weeks after confluence, a time when several
phenotypic variants become prominent. E-cadherin was absent from RPE
cells of fusiform shape but was found in only a subset of epithelioid
RPE cells. Unlike epithelial cell lines expressing E-cadherin, cultured
RPE cells with E-cadherin did not show diminished coexpression of
N-cadherin, increased expression of desmosomal proteins, or a
preferential expression of the
E- (rather than
-N) isoform of the
cadherin linker protein
-catenin. Na/K ATPase distributed to both
apical and basolateral membranes in RPE cells with junctional
E-cadherin and not preferentially to the basolateral domain as in most
epithelial cells with E-cadherin.
CONCLUSIONS. RPE cells express E-cadherin, a cadherin found in most other epithelial cells, but which was believed to be absent from RPE. In RPE in vitro, E-cadherin expression is a late developmental event, occurring in late confluence in cells that already express N-cadherin. E-cadherin is an established epithelial morphoregulatory protein, but it does not induce the same properties in RPE cells as in other epithelial cells, suggesting tissue-specific differences in the potential of E-cadherin to determine an epithelial phenotype.
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