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Abstract
Human renal proximal and distal (thick ascending limb and early distal convoluted
tubule) epithelial cells have been isolated according to their specific antigen expression.
The cells were well characterized by flow cytometry, enzyme cytochemistry and electron
microscopy and cultured for up to 3 months. Cultured tubular cells coexpressed cytokeratin
and vimentin as intermediate filament proteins. While primary isolated cells, proximal
as well as distal, revealed the phenotypic characteristics of their nephron origin,
cultured distal cells showed the tendency to dedifferentiate/transdifferentiate. Distal
cells lost their characteristic expression of Tamm-Horsfall glycoprotein and started
de novo expression of the proximal marker proteins aminopeptidase M, γ-glutamyl transferase
and dipeptidyl peptidase IV. The expression of these antigens by distal cells could
be shown by flow-cytometric analysis and fluorescence microscopy. Enzyme activity
assays revealed the activity of aminopeptidase M, γ-glutamyl transferase and dipeptidyl
peptidase IV, but not of the proximal marker enzyme alkaline phosphatase. This antigenic
shift could not be prevented in different culture media, and the original phenotype
could not be restored. Cultured cells displayed characteristic hormonal stimulation
patterns indicative of their proximal and distal origins, as shown by activation of
adenylate cyclase by different peptide hormones. These results indicate that distal
tubular cells possibly transdifferentiate to a more proximal phenotype in view of
loss of the distal marker enzyme Tamm-Horsfall protein and de novo expression of proximal
marker enzymes like dipeptidyl peptidase IV and aminopeptidase M.