Up-regulation of the tumour-associated marker CD44V6 in experimental kidney disease

CD44 is an adhesion molecule involved in a wide range of cell-cell and cell -matrix interactions. The standard form of CD44 (CD44S) is a 85-90-kD glyco protein, but alternative splicing of RNA encoding 10 variable exons (V1-V10 ) can give rise to many different CD44 variant protein isoforms of higher m olecular weight. CD44 isoforms containing the V6 exon play a crucial role i n tumour metastasis and lymphocyte activation. However, the role of CD44V6 in the kidney is unknown. The aim of this study was to examined renal CD44V 6 expression in health, disease and in vitro. Immunohistochemistry staining with the V6-specific 1.1ASML antibody identified constitutive CD44V6 expre ssion by occasional cortical tubular epithelial cells and medullary tubules in normal rat kidney. In immune-induced kidney disease (rat anti-glomerula r basement membrane glomerulonephritis), there was a marked increase in CD4 4V6 expression by cortical tubules, particularly in areas of tubulointersti tial damage, which was associated with focal macrophage infiltration. There was also a marked increase in CD44V6 expression by damaged tubules in a mo del of non-immune kidney disease (unilateral ureteric obstruction). Reverse transcription-polymerase chain reaction revealed a complex pattern of CD44 V6-containing mRNA isoforms in normal rat kidney. This pattern of CD44V6 sp licing was essentially unaltered in disease. The NRK52E normal rat kidney t ubular epithelial cell line expresses both CD44S and CD44V6. Stimulation of NRK52E cells with IL-1 or transforming growth factor-beta 1 induced a two- to-five-fold increase in the expression of both CD44S and CD44V6. Furthermo re, triggering of NRK52E cells by antibodies to CD44S or CD44V6, but not is otype control antibodies, induced secretion of monocyte chemoattractant pro tein-1. In conclusion, this study has identified expression of the tumour-a ssociated marker CD44V6 in tubular epithelial cells in normal and diseased rat kidney, and suggests that signalling through the CD44V6 molecule may pa rticipate in the pathogenesis of experimental kidney disease.