Glucocorticoid regulation of proteoglycan synthesis in mesangial cells

Mari Kuroda, Hiroyuki Sasamura, Ryoko Shimizu, Mizuo Mifune, Hideaki Nakaya, Emi Kobayashi, Matsuhiko Hayashi, Takao Saruta

Research output: Contribution to journalArticle

16 Citations (Scopus)

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 chondrotin 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.

Original languageEnglish
Pages (from-to)780-789
Number of pages10
JournalKidney International
Volume62
Issue number3
DOIs
Publication statusPublished - 2002

Fingerprint

Mesangial Cells
Proteoglycans
Glucocorticoids
Steroids
Dexamethasone
Biglycan
Decorin
Kidney
Gene Expression
Mifepristone
Ion Exchange
Corticosterone
Prednisolone
Northern Blotting
Sulfates
Gel Chromatography
Permeability
Proteins
Western Blotting
Hormones

Keywords

  • Biglycan
  • Decorin
  • Dexamethasone
  • Glomerular permeability barrier
  • Mesangial matrix
  • Proteoglycans core protein gene
  • Steroid hormones

ASJC Scopus subject areas

  • Nephrology

Cite this

Kuroda, M., Sasamura, H., Shimizu, R., Mifune, M., Nakaya, H., Kobayashi, E., ... Saruta, T. (2002). Glucocorticoid regulation of proteoglycan synthesis in mesangial cells. Kidney International, 62(3), 780-789. https://doi.org/10.1046/j.1523-1755.2002.00524.x

Glucocorticoid regulation of proteoglycan synthesis in mesangial cells. / Kuroda, Mari; Sasamura, Hiroyuki; Shimizu, Ryoko; Mifune, Mizuo; Nakaya, Hideaki; Kobayashi, Emi; Hayashi, Matsuhiko; Saruta, Takao.

In: Kidney International, Vol. 62, No. 3, 2002, p. 780-789.

Research output: Contribution to journalArticle

Kuroda, M, Sasamura, H, Shimizu, R, Mifune, M, Nakaya, H, Kobayashi, E, Hayashi, M & Saruta, T 2002, 'Glucocorticoid regulation of proteoglycan synthesis in mesangial cells', Kidney International, vol. 62, no. 3, pp. 780-789. https://doi.org/10.1046/j.1523-1755.2002.00524.x
Kuroda, Mari ; Sasamura, Hiroyuki ; Shimizu, Ryoko ; Mifune, Mizuo ; Nakaya, Hideaki ; Kobayashi, Emi ; Hayashi, Matsuhiko ; Saruta, Takao. / Glucocorticoid regulation of proteoglycan synthesis in mesangial cells. In: Kidney International. 2002 ; Vol. 62, No. 3. pp. 780-789.
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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 chondrotin 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.",
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