Selective estrogen receptor modulators suppress mesangial cell collagen synthesis

• Published in: American journal of physiology. Renal physiology Vol. 279; no. 2; pp. F309 - F318
• Main Authors: Neugarten, J, Acharya, A, Lei, J, Silbiger, S
• Format: Journal Article
• Language: English
• Published: United States 01.08.2000
• Subjects: Angiotensin II - pharmacology; Animals; Cell Line, Transformed; Collagen - antagonists & inhibitors; Collagen - biosynthesis; Endothelin-1 - pharmacology; Estrogen Receptor beta; Estrogens - pharmacology; Glomerular Mesangium - cytology; Glomerular Mesangium - metabolism; Mice; Mice, Inbred Strains; Mitogen-Activated Protein Kinases - metabolism; Pyrrolidines - pharmacology; Receptors, Estrogen - metabolism; Receptors, Estrogen - physiology; Selective Estrogen Receptor Modulators - pharmacology; Tamoxifen - pharmacology; Thiophenes - pharmacology; Transcription Factor AP-1 - metabolism; Transcription, Genetic - drug effects; Transforming Growth Factor beta - pharmacology; Up-Regulation
• ISSN: 1931-857X; 1522-1466
• DOI: 10.1152/ajprenal.2000.279.2.f309

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.