Beta4 integrin and laminin 5 are aberrantly expressed in polycystic kidney disease: role in increased cell adhesion and migration
| Autor: | Dominique, Joly, Viviane, Morel, Aurélie, Hummel, Antonella, Ruello, Patrick, Nusbaum, Natacha, Patey, Laure-Hélène, Noël, Patricia, Rousselle, Bertrand, Knebelmann |
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| Rok vydání: | 2003 |
| Předmět: |
Adult
Reverse Transcriptase Polymerase Chain Reaction Blotting Western Integrin beta4 Fluorescent Antibody Technique Epithelial Cells Kidney Polycystic Kidney Autosomal Dominant Immunohistochemistry Up-Regulation Cell Movement Cell Adhesion Humans Female Cell Adhesion Molecules Cells Cultured Oligonucleotide Array Sequence Analysis Regular Articles |
| Zdroj: | The American journal of pathology. 163(5) |
| ISSN: | 0002-9440 |
| 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 beta(4) integrin aberrant expression in ADPKD cells. Furthermore, laminin 5 (Ln-5), the main alpha(6)beta(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 alpha(6)beta(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 alpha(6)beta(4) interaction, 2) CC increased haptotactic and chemotactic motility depends on the presence of Ln-5 and requires integrin alpha(3)beta(1) cooperation, and 3) CC haptotactic or chemotactic migration is specifically increased by mAb-mediated beta(4) integrin ligation, through an alpha(3)beta(1) integrin-dependent and independent pathway, respectively. These results highlight the role of Ln-5 and alpha(6)beta(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. |
| Databáze: | OpenAIRE |
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