Murine polycystic kidney epithelial cell lines have increased integrin-mediated adhesion to collagen

Polycystic kidney disease (PKD), in which epithelial cysts arise from or instead of normal renal tubules, is one of the most common genetic diseases. It has both autosomal dominant and autosomal recessive inheritance in humans and in experimental animals. Epithelial cells lining the cysts have an increased rate of proliferation, abnormal polarity of Na-K-adenosinetriphosphatase, which is localized to apical and sometimes lateral membrane domains, and an abnormal extracellular matrix. One hypothesis that explains the simultaneous acquisition of these characteristics as the result of several different genetic mutations is that cell-matrix interactions, which are known to regulate cell proliferation and cell polarity, are altered in PKD. I have created immortalized renal epithelial cell lines from C57Bl/6Jcpk mice with PKD, an autosomal recessive trait in these animals, and from their phenotypically normal littermates. Using these cell lines, I show that polycystic cells have increased adhesion to collagens and laminin mediated by an integrin. These results demonstrate that cell-matrix interactions are defective in PKD and suggest that these interactions may be involved in the abnormalities of cell polarity and cell proliferation seen in these disorders.