Korean J Nephrol.  1998 Jan;17(1):1-7.

The Effect of Cyclic AMP on Gene Regulation of Glomerular Basement Membrane Heparan Sulfate Proteoglycan in Rat Glomerular Epithelial Cells

• Ko CW
• Koo JH
• Park YH

Abstract

It is well known that the glomerular basement membrane heparan sulfate proteoglycan(GBM HSPG) synthesized by glomerular epithelial cell(GEC) has an important role in the permeability of glomerular basement membrane and cyclic AMP(cAMP) is involved in regulation of a wide variety of genes maybe including GBM HSPG gene. The direct effect of cAMP on GBM HSPG gene expression and metabolism was not evaluated as yet. Proteinuria represents an impairment of permselectivity function of glomerular basement membrane regulated by GBM HSPG and could be associated with increased glomerular level of cAMP in nephrotic syndrome of diverse causes. RPD-I(rat GBM HSPG core protein domain-I) detected a >9.5kb transcript of GBM HSPG in RNA of rat GEC. Emp1oying a riboprobe synthesized from RPD-I in RNase protection assay, we examined whether cAMP regulated perlecan expression in the GEC. At l, 6, 24 and 48 hrs of incubation, l mM cAMP caused 43%, 32%, 47% and 40% reduction in mRNA expression of perlecan, respectively. Immunoprecipitation showed a corresponding reduction of 51%, 70% and 68% in the synthesis of 35SO4 labeled GBM HSPG by the GEC fol1owing l2, 24 and 48 hrs of incubation with cAMP. Our results show that decrease in GBM HSPG gene expression and synthesis by cAMP may be of relevance to proteinuric states characterized by activation of these mediators.

Keyword

cAMP; Heparan sulfate proteoglycan; Glomerular epithelial cell

MeSH Terms

Animals
Cyclic AMP*
Epithelial Cells*
Gene Expression
Glomerular Basement Membrane*
Heparan Sulfate Proteoglycans*
Heparitin Sulfate*
Immunoprecipitation
Metabolism
Nephrotic Syndrome
Permeability
Proteinuria
Rats*
Ribonucleases
RNA
RNA, Messenger
Cyclic AMP
Heparan Sulfate Proteoglycans
Heparitin Sulfate
RNA
RNA, Messenger
Ribonucleases