| Popis: |
Extracellular matrix alterations have been suggested to be part of the early events occurring in Autosomal Dominant Polycystic Kidney Disease (ADPKD), a disease characterized by formation of renal cysts and progressive renal failure. Here we report that cDNA array analysis identified β 4 integrin aberrant expression in ADPKD cells. Furthermore, laminin 5 (Ln-5), the main α 6 β 4 integrin ligand, was also found to be abnormally expressed in ADPKD. Studies performed with ADPKD cyst-lining epithelial cells (CC) by comparison with normal tubular cells indicate that integrin α 6 β 4 -Ln-5 interactions are involved in cellular events of potential importance for cystogenesis: 1) laminin 5 is a preferential adhesion substrate for CC, mainly through α 6 β 4 interaction, 2) CC increased haptotactic and chemotactic motility depends on the presence of Ln-5 and requires integrin α 3 β 1 cooperation, and 3) CC haptotactic or chemotactic migration is specifically increased by mAb-mediated β 4 integrin ligation, through an α 3 β 1 integrin-dependent and independent pathway, respectively. These results highlight the role of Ln-5 and α 6 β 4 integrin in adhesive and motility properties of cyst-lining epithelial cells, and further suggest that integrins and extracellular matrix modifications may be of general relevance to kidney epithelial cell cyst formation. |
