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, Darryl R. Peterson

Research output: Contribution to journalArticle

15 Scopus citations

Abstract

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-β 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 αvβ3 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.

Original languageEnglish (US)
Pages (from-to)F710-F723
JournalAmerican Journal of Physiology - Renal Physiology
Volume275
Issue number5 44-5
DOIs
StatePublished - Nov 1998

Keywords

  • Complementary deoxyribonucleic acid cloning
  • Extracellular matrix
  • Fibrillin

ASJC Scopus subject areas

  • Physiology
  • Urology

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    Kanwar, Y. S., Ota, K., Yang, Q., Kumar, A., Wada, J., Kashihara, N., & Peterson, D. R. (1998). Isolation of rat fibrillin-1 cDNA and its relevance in metanephric development. American Journal of Physiology - Renal Physiology, 275(5 44-5), F710-F723. https://doi.org/10.1152/ajprenal.1998.275.5.f710