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 language | English (US) |
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Pages (from-to) | F309-F318 |
Journal | American Journal of Physiology - Renal Physiology |
Volume | 279 |
Issue number | 2 48-2 |
DOIs | |
State | Published - 2000 |
Keywords
- Angiotensin II
- Endothelin
- Estradiol
- Transforming growth factor-β
ASJC Scopus subject areas
- Physiology
- Urology