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      Transdifferentiation of Distal but Not Proximal Tubular Epithelial Cells from Human Kidney in Culture

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          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.

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          Comparative biochemical and immunological studies on gamma-glutamyltransferases from human kidney and renal cell carcinoma applying monoclonal antibodies


            Author and article information

            Nephron Exp Nephrol
            Cardiorenal Medicine
            S. Karger AG
            August 1999
            26 July 1999
            : 7
            : 4
            : 306-313
            aDivision of Nephrology, Department of Internal Medicine IV, J.W. Goethe University, Frankfurt am Main; bDepartment of Urology, Academic Hospital, Offenbach; cDivision of Nephrology, Department of Medicine II, Hospital München-Harlaching, München, Germany
            20618 Exp Nephrol 1999;7:306–313
            © 1999 S. Karger AG, Basel

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            Page count
            Figures: 5, Tables: 1, References: 32, Pages: 8
            Self URI (application/pdf): https://www.karger.com/Article/Pdf/20618
            Original Paper


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