Selective estrogen receptor modulators suppress mesangial cell collagen synthesis

被引：75

作者：

Neugarten, J ^{[1
]}

Acharya, A ^{[1
]}

Lei, J ^{[1
]}

Silbiger, S ^{[1
]}

机构：

[1] Montefiore Med Ctr, Albert Einstein Coll Med, Dept Med, Div Nephrol, Bronx, NY 10467 USA

来源：

AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY | 2000年 / 279卷 / 02期

关键词：

estradiol; angiotensin II; transforming growth factor-beta(1); endothelin;

D O I：

10.1152/ajprenal.2000.279.2.F309

中图分类号：

Q4 [生理学];

学科分类号：

071003 ;

摘要：

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-beta in nanomolar concentrations, suppressed type I and type IV collagen synthesis, suggesting that estrogen receptor-beta 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.

引用

页码：F309 / F318

页数：10

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