ISOLATION OF RAT FIBRILLIN-1 CDNA AND ITS RELEVANCE IN METANEPHRIC DEVELOPMENT

The role of fibrillin-1 in metanephrogenesis was investigated. Fibrill in-1 cDNA was isolated from the rat kidney cDNA Library and sequenced, and its spatiotemporal expression was studied. It had similar to 88% homology with human fibrillin-1 and had Ca2+ binding epidermal growth factor-like domains, transforming growth factor-p binding protein moti fs, and an RGD binding site. Northern blot analysis revealed an simila r to 10-kb transcript, and fibrillin-1 expression was developmentally regulated. In situ hybridization and immunofluorescence studies indica ted that at day 15 of gestation, fibrillin-1 is expressed in the metan ephric mesenchyme. At day 18, its expression was confined to nascent b lood vessels and glomeruli, and it increased in the newborn and neonat al kidneys. Immunoprecipitation revealed an similar to 300-kDa band by SDS-PAGE. Treatment with fibrillin-1 antisense oligodeoxynucleotide i nduced marked dysmorphogenesis of the embryonic metanephroi. Concomita ntly, the fibrillin-1 mRNA, antibody reactivity in the metanephroi, an d fibrillin-1-specific radioincorporation were reduced. These data ind icate that, like alpha(v)beta(3) integrin, a known morphogen and a put ative receptor of fibrillin-1, the fibrillin-1 modulates events relate d to early organogenesis and possibly also the vascularization of the rat kidney.