PGF2alpha induced differential expression of genes involved in turnover of extracellular matrix in rat decidual cells |
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Authors: | Eduardo?A?Callegari Susan?Ferguson-Gottschall Email author" target="_blank">Geula?GiboriEmail author |
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Institution: | (1) Department of Physiology and Biophysics, University of Illinois at Chicago, Chicago, Illinois, USA;(2) Biomedical Resources Infrastructure Network (BRIN), Division of Basic Biomedical Sciences, The University of South Dakota School of Medicine, 414 E. Clark St, 57069 Vermillion, SD, USA |
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Abstract: | In the rat, the decidual tissue is an important component for maternal recognition of pregnancy. Decidualization can be induced
by either the implantation of the blastocyst or by artificial stimuli. The process of decidua formation or decidualization,
is characterized by growth and differentiation of endometrial stromal cells. Prostaglandin F2alpha (PGF2α) has been shown
to be involved in inhibition of implantation, alteration of embryo development, induction of luteal regression, and the mediation
of pregnancy loss induced by microorganism infections. In order to establish a direct role for PGF2α in decidual function,
we have evaluated its effects on the expression of an extensive array of genes using primary decidual cell culture. Upon treatment
with PGF2α sixty genes were significantly down-regulated whereas only six genes were up-regulated (from a total of 1176 genes
studied). Interestingly, the majority of the genes inhibited by PGF2α are either directly or indirectly involved in the turnover
of the extracellular matrix (ECM). Genes such as gelatinase A (MMP2), cathepsin L, tissue inhibitor metalloproteinases 2 (TIMP2)
and 3 (TIMP3), plasminogen activator inhibitor1 (PAI1), tissue type plasminogen activator (tPA), urokinase plasminogen activator
(tPA), endothelin 1, calponin, carboxypeptidase D and calponin acidic were down regulated. The opposite effect was observed
for prostromelysin 53 kDa (proMMP3), plasma proteinase I alpha and alpha 1 antiproteinase, all of which were significantly
up-regulated by PGF2α. The results strongly suggest that the abortificient role of elevated levels of PGF2α after implantation
is due, in large part, to inhibition of genes involved in the normal turnover of the extracellular matrix necessary for decidual
formation. |
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