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Am J Physiol Renal Physiol 275: F710-F723, 1998;
0363-6127/98 $5.00
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Vol. 275, Issue 5, F710-F723, November 1998

Isolation of rat fibrillin-1 cDNA and its relevance in metanephric development

Yashpal S. Kanwar, Kosuke Ota, Qiwei Yang, Anil Kumar, Jun Wada, Naoki Kashihara, and Darryl R. Peterson

Department of Pathology, Northwestern University Medical School, Chicago, Illinois 60611

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 ~88% homology with human fibrillin-1 and had Ca2+ binding epidermal growth factor-like domains, transforming growth factor-beta binding protein motifs, and an RGD binding site. Northern blot analysis revealed an ~10-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 ~300-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 alpha vbeta 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.

fibrillin; complementary deoxyribonucleic acid cloning; extracellular matrix


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