Isolation of rat fibrillin-1 cDNA and its relevance in metanephric development
AJP - Renal Physiology
Isolation of rat fibrillin-1 cDNA and its relevance in metanephric development. Am. J. Physiol. 275 (Renal Physiol. 44): F710-F723, 1998.-The role of fibrillin-1 in metanephrogenesis was investigated. Fibrillin-1 cDNA was isolated from the rat kidney cDNA library and sequenced, and its spatiotemporal expression was studied. It had ϳ88% homology with human fibrillin-1 and had Ca 2ϩ binding epidermal growth factor-like domains, transforming growth factor-␤ binding protein motifs, and an RGD
... g site. Northern blot analysis revealed an ϳ10-kb transcript, and fibrillin-1 expression was developmentally regulated. In situ hybridization and immunofluorescence studies indicated that at day 15 of gestation, fibrillin-1 is expressed in the metanephric mesenchyme. At day 18, its expression was confined to nascent blood vessels and glomeruli, and it increased in the newborn and neonatal kidneys. Immunoprecipitation revealed an ϳ300-kDa band by SDS-PAGE. Treatment with fibrillin-1 antisense oligodeoxynucleotide induced marked dysmorphogenesis of the embryonic metanephroi. Concomitantly, the fibrillin-1 mRNA, antibody reactivity in the metanephroi, and fibrillin-1-specific radioincorporation were reduced. These data indicate that, like ␣ v ␤ 3 integrin, a known morphogen and a putative receptor of fibrillin-1, the fibrillin-1 modulates events related to early organogenesis and possibly also the vascularization of the rat kidney.