Selective estrogen receptor modulators suppress mesangial cell collagen synthesis

Joel Neugarten, Anjali Acharya, Jun Lei, Sharon Silbiger

Research output: Contribution to journalArticle

73 Scopus citations

Abstract

Estrogen receptor modulators (SERMs) are 'designer drugs' that exert estrogen-like actions in some cells but not in others. We examined the effects of the SERMs LY-117018 (an analog of raloxifene) and tamoxifen on mesangial cells synthesis of type I and type IV collagen. We found that LY-117018 and tamoxifen suppressed mesangial cell type IV collagen gene transcription and type IV collagen protein synthesis in a dose-dependent manner, with a potency identical to that of estradiol. Type I collagen synthesis was also suppressed by LY-117018 in a dose-dependent manner with a potency identical to that of estradiol but greater than that of tamoxifen. Genistein, which selectively binds to estrogen receptor-β in nanomolar concentrations, suppressed type I and type IV collagen synthesis, suggesting that estrogen receptor-β mediates the effects of estrogen on collagen synthesis. Because matrix accumulation is central to the development of glomerulosclerosis, second-generation SERMs may prove clinically useful in ameliorating progressive renal disease without the adverse effects of estrogen on reproductive tissues.

Original languageEnglish (US)
Pages (from-to)F309-F318
JournalAmerican Journal of Physiology - Renal Physiology
Volume279
Issue number2 48-2
StatePublished - Sep 18 2000

Keywords

  • Angiotensin II
  • Endothelin
  • Estradiol
  • Transforming growth factor-β

ASJC Scopus subject areas

  • Physiology
  • Urology

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