Alternatively spliced nephrin in experimental glomerular disease of the rat

Nephrin is a novel transmembrane protein of kidney glomerular podocytes, wh ich appears crucially important for the maintenance of the glomerular filtr ation barrier. According to its predicted structure, nephrin has additional roles in cell-cell adhesion and/or signal transduction We have previously cloned the rat homologue of nephrin and described its alternatively spliced transcripts alpha and beta. In this study we examined the alterations in e xpression and regulation of particularly the major alternatively spliced ne phrin-alpha giving rise to a variant lacking the membrane spanning domain i n the puromycin nephrosis of the rat. A down-regulation of up tc, 78% was o bserved of the full length mRNA after 10 d of PAN treatment. The expression changes of nephrin-alpha followed closely the expression of the full lengt h mRNA. Interestingly, we also found nephrin protein in urine at the peak p roteinuria samples of this model. These results suggest that soluble nephri n variants may be important markers for proteinuric diseases.