title: Glucocorticoid regulation of proteoglycan synthesis in mesangial cells.
abstract: BACKGROUND
  Proteoglycans are integral components of the mesangial matrix and glomerular permeability barrier. Recent studies have shown that changes in glomerular proteoglycan expression may play a major role in the pathogenesis of renal disease. Steroid hormones are used as first-choice therapy for the treatment of glomerular diseases, however, the effects of glucocorticoids on expression of glomerular proteoglycans are unknown.
  
  
  METHODS
  This study examined the effects of in vitro and in vivo administration of dexamethasone on proteoglycan synthesis and gene expression of proteoglycan core proteins using rat (RMC) and human (HMC) mesangial cells.
  
  
  RESULTS
  Treatment of cultured RMC with dexamethasone resulted in a dose- and time-dependent decrease (P < 0.05) in both cell-associated and secreted proteoglycan synthesis to approximately 50% of control levels. This effect was inhibited by the glucocorticoid antagonist mifepristone, and mimicked by prednisolone or corticosterone treatment. Separation of proteoglycans by ion-exchange and gel permeation chromatography suggested that chondroitin sulfate/dermatan sulfate proteoglycans were down-regulated after steroid treatment. Northern blot analysis, RT-PCR, Western blot, and promoter activity assays revealed that dexamethasone caused a significant decrease in decorin mRNA (to 61 +/- 8% of controls), whereas biglycan expression and promoter activity were increased after steroid treatment. A similar trend was found in glomeruli isolated from rats treated in vivo with dexamethasone.
  
  
  CONCLUSIONS
  These results demonstrate that treatment of mesangial cells with steroids results in a decrease in total proteoglycan synthesis, as well as subtype-specific changes in proteoglycan core protein gene expression by transcriptional control, furthering our understanding of the effects of steroid treatment on the renal glomeruli.
authors.affiliation: Department of Internal Medicine, School of Medicine, Keio University, 35 Shinanomachi, Tokyo 160-8582, Japan.
authors.forename: Mari
authors.initials: M
authors.lastname: Kuroda
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Sasamura
authors.forename: Ryoko
authors.initials: R
authors.lastname: Shimizu-Hirota
authors.forename: Mizuo
authors.initials: M
authors.lastname: Mifune
authors.forename: Hideaki
authors.initials: H
authors.lastname: Nakaya
authors.forename: Emi
authors.initials: E
authors.lastname: Kobayashi
authors.forename: Matsuhiko
authors.initials: M
authors.lastname: Hayashi
authors.forename: Takao
authors.initials: T
authors.lastname: Saruta
mesh_terms: D053674:Aggrecans; D000818:Animals; D058578:Biglycan; D002478:Cells, Cultured; D058575:Decorin; D003907:Dexamethasone / Q000494:pharmacology*; D016326:Extracellular Matrix Proteins; D015870:Gene Expression / Q000187:drug effects; D005920:Glomerular Mesangium / Q000737:chemistry / Q000166:cytology / Q000502:physiology*; D005938:Glucocorticoids / Q000494:pharmacology*; D006023:Glycoproteins / Q000032:analysis / Q000235:genetics*; D006801:Humans; D037181:Lectins, C-Type; D008297:Male; D011401:Promoter Regions, Genetic / Q000187:drug effects; D011509:Proteoglycans / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: C508321:Acan protein, rat; D053674:Aggrecans; C546884:BGN protein, human; C546886:Bgn protein, rat; D058578:Biglycan; C546878:DCN protein, human; C546880:Dcn protein, rat; D058575:Decorin; D016326:Extracellular Matrix Proteins; D005938:Glucocorticoids; D006023:Glycoproteins; D037181:Lectins, C-Type; D011509:Proteoglycans; D012333:RNA, Messenger; D003907:Dexamethasone