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| Cyclic AMP가 흰쥐 사구체 상피세포의 Heparan Sulfate Proteogllycan 유전자 조절에 미치는 영향 |
| 고철우 , 구자훈 , 박용훈 |
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| Abstract |
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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 glo- merular 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. Employing a riboprobe synthesized from RPD-I in Rnase protection assay, we examined whether cAMP regulated perlecan expression in the GEC. At 1, 6, 24 and 48 hrs of incubation, 1 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 "SO labeled GBM HSPG by the GEC following 12, 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. |
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