Low-dose aspirin protective effects are correlated with deregulation of HNF factor expression in the preeclamptic placentas from mice and humans - Université Paris Cité Accéder directement au contenu
Article Dans Une Revue Cell Death Discovery Année : 2019

Low-dose aspirin protective effects are correlated with deregulation of HNF factor expression in the preeclamptic placentas from mice and humans

Aurélien Ducat
  • Fonction : Auteur
Alexandra Vargas
  • Fonction : Auteur
Ludivine Doridot
  • Fonction : Auteur
Jonathan Lerner
  • Fonction : Auteur
Christophe Buffat
  • Fonction : Auteur
Marco Pontoglio
  • Fonction : Auteur
  • PersonId : 988693
Francisco Miralles

Résumé

Aspirin (acetyl-salicylic acid) is one of the most ancient drugs of the human pharmacopeia. Nonetheless, its action atlow doses is not well understood at the molecular level. One of the applications of low-dose aspirin treatment is theprevention of preeclampsia (PE) in patients at risk. Foeto-placental overexpression of the STOX1A transcription factor inmice triggers PE symptoms. Transcriptomic analysis of the placentas, showed that aspirin massively down-regulatesgenes of the coagulation and complement cascade, as well as genes involved in lipid transport. The genes modifiedby aspirin treatment are not the ones that are modified by STOX1 overexpression, suggesting that aspirin could actdownstream, symptomatically on the preeclamptic disease. Bioinformatics analysis of the promoters of thederegulated genes showed that they are strongly enriched in HNF transcription factors-binding sites, in accordancewith existing literature showing their roles as regulators of coagulation. Two of these transcription factors,Hnf1βandHnf4αare found down-regulated by aspirin treatment. In parallel, we show that in human patient placentas, aspirin-induced deregulations of genes of the coagulation cascade are also observed. Finally, the expression of Hnf1βtargetsequences (Kif12,F2,Hnf4αpromoters and a synthetic concatemer of the Hnf1β-binding site) were investigated bytransfection in trophoblast cell models, with or without aspirin treatment and with or without STOX1A overexpression.In this model we observed that STOX1A and aspirin tended to synergize in the down-regulation of Hnf1βtarget genesin trophoblasts.
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hal-02349216 , version 1 (26-05-2020)

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Aurélien Ducat, Alexandra Vargas, Ludivine Doridot, Alessia A Bagattin, Jonathan Lerner, et al.. Low-dose aspirin protective effects are correlated with deregulation of HNF factor expression in the preeclamptic placentas from mice and humans. Cell Death Discovery, 2019, 5 (1), ⟨10.1038/s41420-019-0170-x⟩. ⟨hal-02349216⟩
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