Cloning of mouse integrin α_v cDNA and role of the α_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 α and β subunits and are present in various tissues in different heterodimeric forms. In this study, one of the members of the integrin superfamily, α_v, was characterized, and its relevance in murine nephrogenesis was investigated. Mouse embryonic renal cDNA libraries were prepared and screened for α_v, and multiple clones were isolated and sequenced. The deduced amino acid sequence of the α_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)_nA mRNA instability motifs were present. Conformational analysis revealed no rigid long-range-ordered structure in murine α_v. The α_v was expressed in the embryonic kidney at day 13 of the gestation, with a transcript size of ∼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 α_v, i.e., with β¹, β³, β₅, and β₆, were observed in metanephric tissues. Inclusion of α_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 α_v. The expressions of integrin β₃, β₅, and β₆ were unaltered. These findings suggest that the integrin α_v is developmentally regulated, has a distinct spatio-temporal expression, and is relevant in the mammalian organogenesis.