Differentiation of trophoblast giant cells and their metabolic functions are dependent on peroxisome proliferator-activated receptor beta/delta.
Data(s) |
2006
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Resumo |
Mutation of the nuclear receptor peroxisome proliferator-activated receptor beta/delta (PPARbeta/delta) severely affects placenta development, leading to embryonic death at embryonic day 9.5 (E9.5) to E10.5 of most, but not all, PPARbeta/delta-null mutant embryos. While very little is known at present about the pathway governed by PPARbeta/delta in the developing placenta, this paper demonstrates that the main alteration of the placenta of PPARbeta/delta-null embryos is found in the giant cell layer. PPARbeta/delta activity is in fact essential for the differentiation of the Rcho-1 cells in giant cells, as shown by the severe inhibition of differentiation once PPARbeta/delta is silenced. Conversely, exposure of Rcho-1 cells to a PPARbeta/delta agonist triggers a massive differentiation via increased expression of 3-phosphoinositide-dependent kinase 1 and integrin-linked kinase and subsequent phosphorylation of Akt. The links between PPARbeta/delta activity in giant cells and its role on Akt activity are further strengthened by the remarkable pattern of phospho-Akt expression in vivo at E9.5, specifically in the nucleus of the giant cells. In addition to this phosphatidylinositol 3-kinase/Akt main pathway, PPARbeta/delta also induced giant cell differentiation via increased expression of I-mfa, an inhibitor of Mash-2 activity. Finally, giant cell differentiation at E9.5 is accompanied by a PPARbeta/delta-dependent accumulation of lipid droplets and an increased expression of the adipose differentiation-related protein (also called adipophilin), which may participate to lipid metabolism and/or steroidogenesis. Altogether, this important role of PPARbeta/delta in placenta development and giant cell differentiation should be considered when contemplating the potency of PPARbeta/delta agonist as therapeutic agents of broad application. |
Identificador |
http://serval.unil.ch/?id=serval:BIB_8549A418D681 isbn:0270-7306[print], 0270-7306[linking] pmid:16581799 doi:10.1128/MCB.26.8.3266-3281.2006 isiid:000236657600036 |
Idioma(s) |
en |
Fonte |
Molecular and Cellular Biology, vol. 26, no. 8, pp. 3266-3281 |
Palavras-Chave | #1-Phosphatidylinositol 3-Kinase/metabolism; Animals; Cell Differentiation; Cell Nucleus/metabolism; Cells, Cultured; Female; Genetic Vectors; Giant Cells/metabolism; Giant Cells/physiology; Lipids/biosynthesis; Mice; Mice, Inbred C57BL; Mice, Knockout; Models, Biological; PPAR delta/genetics; PPAR delta/metabolism; PPAR-beta/genetics; PPAR-beta/metabolism; Peptides/metabolism; Pregnancy; Proto-Oncogene Proteins c-akt/metabolism; Transformation, Genetic; Trophoblasts/metabolism; Trophoblasts/physiology |
Tipo |
info:eu-repo/semantics/article article |