Jung Han Lee1, Yan Wen, Mary Lake Polan, Bertha Chen. 1. Department of Obstetrics and Gynecology, Hanyang University, School of Medicine, 17 Haengdang-dong, Seongdong-gu, Seoul 133-791, Republic of Korea.
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.
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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