Developmental regulation of ksp-cadherin expression in the human kidney

Cell adhesion molecules, including the cadherins, are important regulators of cellular differentiation and proliferation. Ksp-cadherin, a novel member of the cadherin family, is expressed only in the kidney (Thomson a al, 1. Biol. Chetn. 270:17594,1995). Monoclonal antibodies were generated against the C-terminal 266 amino acid residues of human Ksp-cadherin fused to a maltose-binding-protein. Two antibodies were found to specifically react with the cadherin portion of the fusion protein, and one, 4H6, was used for subsequent studies. Specificity of this antibody was confirmed by Western blot analysis demonstrating labeling of a 130 kDa protein in L-cells transfected with human Ksp-cadherin. The labeled protein in transfected cells was identical in size to that labeled in native human kidney membranes. Monoclonal antibody 4H6 was used to characterize the expression of Ksp-cadherin in formalin-fixed, paraffin-embedded human kidney sections. By immunofluorescence microscopy, Ksp-cadherin was detected on the basolateral membrane of multiple segments of the nephron. In the cortical region, staining of distal tubules was strong, whereas staining of proximal tubules was variable and of weaker intensity. Intermediate staining was found in cortical collecting ducts. No staining was detected in the glomeruli. In the medullary regions, thick ascending limbs of the loop of Henle had a higher level of staining than collecting ducts. We also characterized Ksp-cadherin expression during human kidney maturation by studying tissue sections from 14 to 20 weeks of fetal development In general, there was a gradient of staining, with greater labeling of the more differentiated structures. Staining was greatest for collecting tubules, intermediate for ureteric ducts, and minimal for ampullae of ureteric buds. Staining of renal vesicles, comma-shaped bodies, and Sshaped bodies was also minimal. In conclusion, Ksp-cadherin is expressed on the basolateral membrane of virtually all tubular segments or the adult human kidney. In the developing kidney, the protein is principally expressed in more mature structures. Thus, Ksp-cadherin may play a role in maintaining rather than guiding tubular differentiation.