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.
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Funding
This work was supported by the National Institute of Aging at the National Institutes of Health [RO1 AG01790] and the Mary Lake Polan Transition Fund of the Stanford University School of Medicine.
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Jung Han Lee and Yan Wen contributed equally as first authors.
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Lee, J.H., Wen, Y., Polan, M.L. et al. The effect of raloxifene, a SERM, on extracellular matrix protein expression of pelvic fibroblasts. Int Urogynecol J 23, 349–355 (2012). https://doi.org/10.1007/s00192-011-1567-0
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DOI: https://doi.org/10.1007/s00192-011-1567-0