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Inhibition of Histone Deacetylase Activity in Human Endometrial Stromal Cells Promotes Extracellular Matrix Remodelling and Limits Embryo Invasion

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Inhibition of Histone Deacetylase Activity in Human Endometrial Stromal Cells Promotes Extracellular Matrix Remodelling and Limits Embryo Invasion

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dc.contributor.author Estella Sagrado, Carlos es_ES
dc.contributor.author Herrer Mambrona, Isabel es_ES
dc.contributor.author Atkinson, Stuart P. es_ES
dc.contributor.author Quiñonero, Alicia es_ES
dc.contributor.author Martínez, Sebastián es_ES
dc.contributor.author Pellicer Martínez, Antonio es_ES
dc.contributor.author Simón Vallés, Carlos es_ES
dc.date.accessioned 2015-06-19T10:18:00Z
dc.date.available 2015-06-19T10:18:00Z
dc.date.issued 2012 es_ES
dc.identifier.citation PLoS ONE Vol. 7 Issue 1: es_ES
dc.identifier.uri http://hdl.handle.net/10550/44546
dc.description.abstract Invasion of the trophoblast into the maternal decidua is regulated by both the trophoectoderm and the endometrial stroma, and entails the action of tissue remodeling enzymes. Trophoblast invasion requires the action of metalloproteinases (MMPs) to degrade extracellular matrix (ECM) proteins and in turn, decidual cells express tissue inhibitors of MMPs (TIMPs). The balance between these promoting and restraining factors is a key event for the successful outcome of pregnancy. Gene expression is post-transcriptionally regulated by histone deacetylases (HDACs) that unpacks condensed chromatin activating gene expression. In this study we analyze the effect of histone acetylation on the expression of tissue remodeling enzymes and activity of human endometrial stromal cells (hESCs) related to trophoblast invasion control. Treatment of hESCs with the HDAC inhibitor trichostatin A (TSA) increased the expression of TIMP-1 and TIMP-3 while decreased MMP-2, MMP-9 and uPA and have an inhibitory effect on trophoblast invasion. Moreover, histone acetylation is detected at the promoters of TIMP-1 and TIMP-3 genes in TSA-treated. In addition, in an in vitro decidualized hESCs model, the increase of TIMP-1 and TIMP-3 expression is associated with histone acetylation at the promoters of these genes. Our results demonstrate that histone acetylation disrupt the balance of ECM modulators provoking a restrain of trophoblast invasion. These findings are important as an epigenetic mechanism that can be used to control trophoblast invasion. es_ES
dc.title Inhibition of Histone Deacetylase Activity in Human Endometrial Stromal Cells Promotes Extracellular Matrix Remodelling and Limits Embryo Invasion es_ES
dc.type journal article es_ES
dc.identifier.doi 10.1371/journal.pone.0030508 es_ES
dc.identifier.idgrec 081497 es_ES

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