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      mRNA Differential Display Analysis of Nephrotic Kidney Glomeruli

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          Background: Differential display RT-PCR (DDRT-PCR) is a new powerful technique for identification and characterization of altered gene expression in eukaryotic cells and tissues. We studied here changes in kidney glomerular gene expression in patients with congenital nephrotic syndrome of the Finnish type (CNF), an inherited kidney disease with heavy proteinuria already in utero. Methods: Using the DDRT-PCR approach and isolated glomeruli from removed human kidneys, we compared the gene expression patterns of normal human and CNF glomeruli. Differential expression of candidate genes was verified by Northern blotting, and the corresponding PCR fragments were sequenced and compared to known sequences in databanks. Results: We found several genes and sequence tags with altered expression in nephrotic glomeruli including fragments with close homologies to cytochrome c oxidase subunit I, integrin-linked kinase, insulin-like growth factor II receptor and eotaxin, and also clones resembling anchyrin and cadherin-like consensus sequences. Conclusion: All the sequences identified are of interest in respect to pathogenesis of proteinuria. Furthermore, this study reveals potentially new members to known gene families with tissue and cell type-specific expression.

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          Isolation and cDNA cloning of Ksp-cadherin, a novel kidney-specific member of the cadherin multigene family.

          Cadherins are recognized as the principal mediators of homotypic cellular recognition and play a demonstrated role in the morphogenic direction of tissue development. We report here the identification of a structurally unique, kidney-specific member of the cadherin multigene family (Ksp-cadherin). cDNA cloning and molecular analysis of the 130-kDa protein confirmed that it was novel and indicated that it most closely resembled members of the LI-cadherin/HPT-1 cadherin subgroup. The predicted protein possesses the definitive cadherin-specific sequence motifs LDRE, DXND, and DXD in well conserved sequential arrangement, and the characteristic cysteine residues found in the last ectodomains of almost all known cadherins. Like LI-cadherin and HPT-1, Ksp-cadherin lacks the prosequence and HAV adhesion recognition sequence typical of most classical cadherins, and possesses a truncated cytoplasmic domain (18-22 amino acids). When expressed in a transient Vaccinia/T7 expression system, Ksp-cadherin displayed the classic calcium sensitivity to trypsin proteolysis that is observed in all cadherins. Immunolocalization studies and Northern analysis indicated that expression of Ksp-cadherin was kidney-specific and limited to the basolateral membranes of renal tubular epithelial cells. In summary, we have identified and cloned a novel, kidney-specific member of the cadherin multigene family that we propose be designated Ksp-cadherin.
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            Glucose Increases Both the Plasma Membrane Number and Phosphorylation of Insulin-like Growth Factor II/Mannose 6-Phosphate Receptors

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              • Abstract: not found
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              Glomerular basement membrane collagen and activities of the intracellular enzymes of collagen biosynthesis in congenital nephrotic syndrome of the Finnish type


                Author and article information

                Nephron Exp Nephrol
                Cardiorenal Medicine
                S. Karger AG
                February 1999
                14 January 1999
                : 7
                : 1
                : 52-58
                aHaartman Institute, Division of Bacteriology and Immunology, University of Helsinki, Finland, and bMedical Policlinic, University of Munich, Germany
                20584 Exp Nephrol 1999;7:52–58
                © 1999 S. Karger AG, Basel

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                Figures: 3, Tables: 1, References: 40, Pages: 7
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