Proteinuria in diabetic nephropathy has been correlated with reduction in heparan sulfate proteoglycan (HSPG) content of the glomerular basement membrane. We have previously shown that the underlying mechanism probably involves reduction in the synthesis by glomerular epithelial cells. In this study we explored whether high glucose medium regulates basement membrane HSPG gene expression. Northern analysis demonstrated that rat glomerular epithelial cells in vitro constitutively express mRNA for basement membrane HSPG, similar to that observed in rat kidney glomerulus. RNase protection assay showed that incubation of glomerular epithelial cells with 30 mM glucose for 24 h and 7 days resulted in reduction in HSPG mRNA abundance. The decrease in mRNA abundance correlated with reduction in the synthesis of 35S04-labeled basement membrane HSPG as measured by immunoprecipitation. Reduction in synthesis of HSPG could not be entirely accounted for by decrease in mRNA abundance, suggesting both transcriptional and posttranscriptional mechanisms may be involved in reduction of glomerular basement membrane HSPG synthesis by glomerular epithelial cells in diabetic nephropathy.
|Original language||English (US)|
|Number of pages||6|
|Journal||Journal of Cellular Physiology|
|State||Published - Apr 1996|
ASJC Scopus subject areas
- Clinical Biochemistry
- Cell Biology