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

被引:14
作者
Kanwar, YS [1 ]
Ota, K [1 ]
Yang, QW [1 ]
Kumar, A [1 ]
Wada, J [1 ]
Kashihara, N [1 ]
Peterson, DR [1 ]
机构
[1] Northwestern Univ, Sch Med, Dept Pathol, Chicago, IL 60611 USA
关键词
fibrillin; complementary deoxyribonucleic acid cloning; extra-cellular matrix;
D O I
10.1152/ajprenal.1998.275.5.F710
中图分类号
Q4 [生理学];
学科分类号
071003 ;
摘要
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 similar to 88% homology with human fibrillin-1 and had Ca(2+) binding epidermal growth factor-like domains, transforming growth factor-p binding protein motifs, and an RGD binding site. Northern blot analysis revealed an similar to 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 similar to 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(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.
引用
收藏
页码:F710 / F723
页数:14
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