[Gene expression of heparanase in peripheral blood leukocytes from rats with nephrotic syndrome and its relationship to proteinuria].

OBJECTIVE

The beta-D-endoglycosidase heparanase (Hpa) is HS-specific which leads to heparan sulfate (HS) degradation. An increased permeability of the glomerular basement membrane (GBM) for proteinuria is related with a decreased HS side chains of the GBM. However, whether an up-regulated expression of Hpa exists in nephrotic syndrome (NS) remains unknown. The purpose of this study was to evaluate the role of Hpa in the development of NS and the relevance to proteinuria.

METHODS

NS was induced in SD rats by tail intravenous injection of 5 mg/kg Adriamycin. Rats were housed in the metabolic cages for 24 hours to collect urine prior to induction of disease and at day 7 and 14 following disease induction. By using the method of reverse transcriptase-PCR (RT-PCR), Hpa gene from the peripheral blood leukocytes of these rats was assayed.

RESULTS

The resulting cDNA fragment was consistent with rat heparanase mRNA sequence in GenBank (accession number AF184963). The rats at day 7 and 14 showed significantly up-regulated Hpa mRNA expression in contrast to the normal rats. There was a significant correlation between the level of Hpa mRNA and the quantification of urinary protein (r=0.925, P<0.001).

CONCLUSION

Up-regulated expression of Hpa mRNA may be an important contributor to loss of glomerular negative charge in GBM and hence may lead to proteinuria in nephrotic syndrome.