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The nuclear factor-κB pathway is involved in matrix metalloproteinase-9 expression in RU486-induced endometrium breakdown in mice.
Hum Reprod. 2012 Jul; 27(7):2096-106.HR

Abstract

BACKGROUND

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-κB (NF-κB) 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-κB 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-κB to MMP9 gene promoter. Inhibitors of NF-κB were used to block its signal in vivo and in vitro to analyze the function of NF-κB in the tissue breakdown process.

RESULTS

Administration of RU486 resulted in increased phospho-IκB levels and nuclear translocation of p65 in decidual stromal cells, accompanied by the up-regulation of NF-κB inducing kinase and IκB kinase β mRNA. The NF-κB 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-κB activation and inhibition, respectively. RU486 stimulated recruitment of NF-κB p65 to the MMP9 promoter and further increased its expression. Effects of NF-κB 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-κB 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.

Authors+Show Affiliations

Graduate School of Peking Union Medical College, Beijing 100730, People's Republic of China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22587999

Citation

Li, Yun-Feng, et al. "The Nuclear factor-κB Pathway Is Involved in Matrix Metalloproteinase-9 Expression in RU486-induced Endometrium Breakdown in Mice." Human Reproduction (Oxford, England), vol. 27, no. 7, 2012, pp. 2096-106.
Li YF, Xu XB, Chen XH, et al. The nuclear factor-κB pathway is involved in matrix metalloproteinase-9 expression in RU486-induced endometrium breakdown in mice. Hum Reprod. 2012;27(7):2096-106.
Li, Y. F., Xu, X. B., Chen, X. H., Wei, G., He, B., & Wang, J. D. (2012). The nuclear factor-κB pathway is involved in matrix metalloproteinase-9 expression in RU486-induced endometrium breakdown in mice. Human Reproduction (Oxford, England), 27(7), 2096-106. https://doi.org/10.1093/humrep/des110
Li YF, et al. The Nuclear factor-κB Pathway Is Involved in Matrix Metalloproteinase-9 Expression in RU486-induced Endometrium Breakdown in Mice. Hum Reprod. 2012;27(7):2096-106. PubMed PMID: 22587999.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The nuclear factor-κB pathway is involved in matrix metalloproteinase-9 expression in RU486-induced endometrium breakdown in mice. AU - Li,Yun-Feng, AU - Xu,Xiang-Bo, AU - Chen,Xi-Hua, AU - Wei,Gang, AU - He,Bin, AU - Wang,Jie-Dong, Y1 - 2012/05/15/ PY - 2012/5/17/entrez PY - 2012/5/17/pubmed PY - 2012/11/14/medline SP - 2096 EP - 106 JF - Human reproduction (Oxford, England) JO - Hum Reprod VL - 27 IS - 7 N2 - BACKGROUND: 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-κB (NF-κB) 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-κB 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-κB to MMP9 gene promoter. Inhibitors of NF-κB were used to block its signal in vivo and in vitro to analyze the function of NF-κB in the tissue breakdown process. RESULTS: Administration of RU486 resulted in increased phospho-IκB levels and nuclear translocation of p65 in decidual stromal cells, accompanied by the up-regulation of NF-κB inducing kinase and IκB kinase β mRNA. The NF-κB 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-κB activation and inhibition, respectively. RU486 stimulated recruitment of NF-κB p65 to the MMP9 promoter and further increased its expression. Effects of NF-κB 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-κB 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. SN - 1460-2350 UR - https://www.unboundmedicine.com/medline/citation/22587999/The_nuclear_factor_κB_pathway_is_involved_in_matrix_metalloproteinase_9_expression_in_RU486_induced_endometrium_breakdown_in_mice_ L2 - https://academic.oup.com/humrep/article-lookup/doi/10.1093/humrep/des110 DB - PRIME DP - Unbound Medicine ER -