Cloning of mouse integrin alpha(V) cDNA and role of the alpha(V)-related matrix receptors in metanephric development

Metanephrogenesis has been a long-standing model to study cell-matrix interactions. A number of adhesion molecules, including matrix receptors (i.e., integrins), are believed to be involved in such interactions. The integrins contain alpha and beta subunits and are present in various tissues in different heterodimeric forms. In this study, one of the members of the integrin superfamily, alpha(v), was characterized, and its relevance in murine nephrogenesis was investigated. Mouse embryonic renal cDNA libraries were prepared and screened for alpha(v), and multiple clones were isolated and sequenced. The deduced amino acid sequence of the alpha(v) cDNA clones and hydropathic analysis revealed that it has a typical signal sequence and extracellular, transmembrane, and cytoplasmic domains, with multiple Ca2+ binding sites. No A(U)(n)A mRNA instability motifs were present. Conformational analysis revealed no rigid long-range-ordered structure in murine alpha v. The alpha(v) was expressed in the embryonic kidney at day 13 of the gestation, with a transcript size of similar to 7 kb. Its expression increased progressively during the later gestational stages and in the neonatal period. It was distributed in the epithelial elements of developing nephrons and was absent in the uninduced mesenchyme. In mature metanephroi, the expression was relatively high in the glomeruli and blood vessels, as compared to the tubules. Various heterodimeric associations of alpha(v), i.e., with beta(1), beta(3), beta(5), and beta(6), were observed in metanephric tissues. Inelusion of alpha(v)-antisense-oligodeoxynucleotide or -antibody in metanephric culture induced dysmorphogenesis of the kidney with reduced population of the nephrons, disorganization of the ureteric bud branches, and reduction of mRNA and protein expressions of alpha(v). The expressions of integrin beta(3), beta(5), and beta(6) were unaltered. These findings suggest that the integrin alpha(v) is developmentally regulated, has a distinct spatio-temporal expression, and is relevant in the mammalian organogenesis.