The effect of raloxifene, a SERM, on extracellular matrix protein expression of pelvic fibroblasts.

Abstract

INTRODUCTION AND HYPOTHESIS:

We hypothesize that the abnormal extracellular matrix (ECM) turnover in pelvic tissues of women with prolapse may be attenuated by raloxifene. We examine the effect of raloxifene on ECM protein expression in pelvic fibroblasts.

METHODS:

Pelvic fibroblasts were isolated from cases (N = 6) and controls (N = 3). Cells were treated with raloxifene. Dose-response analyses were performed by ANOVA. mRNA and protein expression of collagen I, III, MMPs, and TIMPs were determined by RT-PCR and Western blot. MMP activity was analyzed by zymography.

RESULTS:

The mRNA expression of TIMP-3 and protein expression of TIMP-1 and TIMP-3 were significantly increased by raloxifene in fibroblasts from both cases and controls (P < 0.05). Collagen I, III, and MMP mRNA and protein expressions were not affected.

CONCLUSIONS:

Raloxifene selectively attenuates abnormal matrix degradation by increasing inhibitors of proteases, TIMPs, in pelvic fibroblasts. This opens the possibility for SERMs to be used as preventive therapy for pelvic floor disorders.

• Authors: Jung Han Lee, Yan Wen, Mary Lake Polan, Bertha Chen
• Journal: International urogynecology journal (Int Urogynecol J) Vol. 23 Issue 3 Pg. 349-55 (Mar 2012) ISSN: 1433-3023 [Electronic] England
• PMID: 21935668 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Collagen Type I
• Collagen Type III
• Extracellular Matrix Proteins
• Selective Estrogen Receptor Modulators
• Tissue Inhibitor of Metalloproteinases
• Raloxifene Hydrochloride
• Matrix Metalloproteinases

Topics

• Aged
• Blotting, Western
• Cells, Cultured
• Collagen Type I (metabolism)
• Collagen Type III (metabolism)
• Drug Evaluation, Preclinical
• Electrophoresis, Polyacrylamide Gel
• Extracellular Matrix Proteins (metabolism)
• Female
• Fibroblasts (drug effects, enzymology)
• Humans
• Matrix Metalloproteinases (metabolism)
• Middle Aged
• Pelvic Floor Disorders (enzymology, prevention & control)
• Polymerase Chain Reaction
• Raloxifene Hydrochloride (pharmacology, therapeutic use)
• Selective Estrogen Receptor Modulators (pharmacology, therapeutic use)
• Tissue Inhibitor of Metalloproteinases (metabolism)