Abstract |
Effects of progesterone receptor modulator CDB-2914 on the expression of the extracellular matrix (ECM) components were examined in cultured human uterine leiomyoma and myometrial cells. ECM metalloproteinase inducer ( EMMPRIN), matrix metalloproteinases ( MMPs), tissue inhibitors of MMP (TIMPs) and collagen levels were assessed by Western blot analysis, MMP activity assay and real-time RT-PCR. RNA interference (RNAi) of EMMPRIN was performed using small interfering mRNA. In cultured leiomyoma cells, CDB-2914 treatment at concentrations greater than or equal to 10(-8) M significantly increased EMMPRIN, MMP-1 and MMP-8 protein contents and MMP-1, MMP-2, MMP-3 and MMP-9 mRNA levels, and activity of MMP-1, MMP-2, MMP-3 and MMP-9 in the medium. TIMP-1 and TIMP-2 were significantly decreased at mRNA and protein levels by CDB-2914 treatment at concentrations > or =10(-7) M in these cells. CDB-2914 treatment decreased types I and III collagen protein contents. However, CDB-2914 treatment did not affect the ECM component expression in cultured myometrial cells. RNAi of EMMPRIN abrogated CDB-2914-mediated both induction of MMPs and reduction of TIMPs and collagens in cultured leiomyoma cells. These results suggest that CDB-2914 modulates the expression of EMMPRIN, MMPs, TIMPs and collagens in cultured leiomyoma cells without comparable effects on myometrial cells.
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Authors | Qin Xu, Noriyuki Ohara, Jin Liu, Mariko Amano, Regine Sitruk-Ware, Shigeki Yoshida, Takeshi Maruo |
Journal | Molecular human reproduction
(Mol Hum Reprod)
Vol. 14
Issue 3
Pg. 181-91
(Mar 2008)
ISSN: 1460-2407 [Electronic] England |
PMID | 18216291
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- BSG protein, human
- Norpregnadienes
- RNA, Small Interfering
- Receptors, Progesterone
- Tissue Inhibitor of Metalloproteinase-1
- Tissue Inhibitor of Metalloproteinase-2
- Basigin
- ulipristal
- Matrix Metalloproteinases
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Topics |
- Adult
- Basigin
(genetics, metabolism)
- Blotting, Western
- Cells, Cultured
- Female
- Humans
- Leiomyoma
(genetics, metabolism, pathology)
- Matrix Metalloproteinases
(genetics, metabolism)
- Middle Aged
- Myometrium
(drug effects, metabolism)
- Norpregnadienes
(pharmacology)
- RNA, Small Interfering
(genetics)
- Receptors, Progesterone
(antagonists & inhibitors)
- Reverse Transcriptase Polymerase Chain Reaction
- Tissue Inhibitor of Metalloproteinase-1
(genetics, metabolism)
- Tissue Inhibitor of Metalloproteinase-2
(genetics, metabolism)
- Tumor Cells, Cultured
- Uterine Neoplasms
(metabolism, pathology)
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