Isolation of rat fibrillin-1 cdna and its relevance in metanephric
development.
Kanwar, Yashpal S., Kosuke Ota, Qiwei Yang, Anil Kumar, Jun Wada,
Naoki Kashihara, and Darryl R. Peterson.
Department of Pathology, Northwestern University Medical School,
Chicago, Illinois 60611
APStracts 5:0146F, 1998.
Role of fibrillin-1 in metanephrogenesis was investigated. Fibrillin-1
cDNA was isolated from rat kidney cDNA library, sequenced, and its
spatio-temporal expression was studied. It had (88% homology with
human fibrillin-1, and had Ca++ binding epidermal growth factor like
domains, TGF-[beta] binding protein motifs and a RGD binding site.
Northern blot analysis revealed a (10kb 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 a (300 kd 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]v[beta]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.
Received 20 May 1998; accepted in final form 20 August 1998.
APS Manuscript Number F125-8.
Article publication pending Am. J. Physiol. (Renal Physiology).
ISSN 1080-4757 Copyright 1998 The American Physiological Society.
Published in APStracts on 21 September 1998