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ArtikelThe nuclear factor-?B pathway is involved in matrix metalloproteinase-9 expression in RU486-induced endometrium breakdown in mice  
Oleh: Li, Yun-Feng ; Xu, Xiang-Bo ; Chen, Xi-Hua ; Wei, Gang
Jenis: Article from Journal - ilmiah internasional
Dalam koleksi: Human Reproduction vol. 27 no. 07 (Jul. 2012), page 2096-2106.
Topik: REPRODUCTIVE BIOLOGY; NF-?B; MMP9; progesterone withdrawal; tissue breakdown; mifepristone
Ketersediaan
  • Perpustakaan FK
    • Nomor Panggil: H07.K.2012.02
    • Non-tandon: 1 (dapat dipinjam: 0)
    • Tandon: tidak ada
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Isi artikelBACKGROUND Progesterone-withdrawal (WP)-induced endometrial breakdown occurs in both physiological and pathological processes such as menstruation and abortion. However, the underlying mechanisms are not clearly understood. As the nuclear factor-?B (NF-?B) pathway has been proposed to play a role in endometrial breakdown, we tested this hypothesis using RU486-induced mouse menstruation-like model. METHODS The activation of NF-?B was evaluated by immunohistochemistry, western blot and immunofluorescence. The expression of matrix metalloproteinase-9 (MMP9) was analyzed by real-time PCR and its proteins by gelatin zymography and western blot. Chromatin immunoprecipitation was used to investigate the direct binding of NF-?B to MMP9 gene promoter. Inhibitors of NF-?B were used to block its signal in vivo and in vitro to analyze the function of NF-?B in the tissue breakdown process. RESULTS Administration of RU486 resulted in increased phospho-I?B levels and nuclear translocation of p65 in decidual stromal cells, accompanied by the up-regulation of NF-?B inducing kinase and I?B kinase ß mRNA. The NF-?B inhibitor, ‘pyrrolidine dithiocarbamate’ partially suppressed the RU486-induced endometrial breakdown, thus verifying the role of this pathway in vivo. MMP9 was up- and down-regulated following the NF-?B activation and inhibition, respectively. RU486 stimulated recruitment of NF-?B p65 to the MMP9 promoter and further increased its expression. Effects of NF-?B activation and inactivation on MMP9 expression were further explored in human stromal cells in vitro. A similar MMP9 expression pattern was observed in cultured human, as well as mouse, decidual stromal cells following RU486 treatment. CONCLUSIONS The activation of the NF-?B pathway induces downstream target genes, including MMP9 from stromal cells to facilitate tissue breakdown in mouse uterus, highlighting the likelihood that this regulatory pattern exists in the human endometrium.
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