Selective estrogen receptor modulators suppress mesangial cell collagen synthesis

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-1...

Full description

Saved in:
Bibliographic Details
Published in:American journal of physiology. Renal physiology 2000-08, Vol.279 (2), p.F309-F318
Main Authors: Neugarten, J, Acharya, A, Lei, J, Silbiger, S
Format: Article
Language:English
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
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:1931-857X
1522-1466
DOI:10.1152/ajprenal.2000.279.2.f309