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Annexin A1/Formyl Peptide Receptor Pathway Controls Uterine Receptivity to the Blastocyst.
Hebeda, Cristina B; Sandri, Silvana; Benis, Cláudia M; Paula-Silva, Marina de; Loiola, Rodrigo A; Reutelingsperger, Chris; Perretti, Mauro; Farsky, Sandra H P.
Afiliação
  • Hebeda CB; Department of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, University of Sao Paulo, São Paulo CEP 05508-000, Brazil.
  • Sandri S; Department of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, University of Sao Paulo, São Paulo CEP 05508-000, Brazil.
  • Benis CM; Department of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, University of Sao Paulo, São Paulo CEP 05508-000, Brazil.
  • Paula-Silva M; Department of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, University of Sao Paulo, São Paulo CEP 05508-000, Brazil.
  • Loiola RA; Department of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, University of Sao Paulo, São Paulo CEP 05508-000, Brazil.
  • Reutelingsperger C; Faculty of Health, Medicine and Life Sciences, Part of Maastricht University Medical Center, Part of Maastricht University, 6211 LK Maastricht, The Netherlands.
  • Perretti M; The William Harvey Research Institute, Queen Mary University of London, London EC1M 6BQ, UK.
  • Farsky SHP; Department of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, University of Sao Paulo, São Paulo CEP 05508-000, Brazil.
Cells ; 9(5)2020 05 11.
Article em En | MEDLINE | ID: mdl-32403233
Embryo implantation into the uterine wall is a highly modulated, complex process. We previously demonstrated that Annexin A1 (AnxA1), which is a protein secreted by epithelial and inflammatory cells in the uterine microenvironment, controls embryo implantation in vivo. Here, we decipher the effects of recombinant AnxA1 in this phenomenon by using human trophoblast cell (BeWo) spheroids and uterine epithelial cells (Ishikawa; IK). AnxA1-treated IK cells demonstrated greater levels of spheroid adherence and upregulation of the tight junction molecules claudin-1 and zona occludens-1, as well as the glycoprotein mucin-1 (Muc-1). The latter effect of AnxA1 was not mediated through IL-6 secreted from IK cells, a known inducer of Muc-1 expression. Rather, these effects of AnxA1 involved activation of the formyl peptide receptors FPR1 and FPR2, as pharmacological blockade of FPR1 or FPR1/FPR2 abrogated such responses. The downstream actions of AnxA1 were mediated through the ERK1/2 phosphorylation pathway and F-actin polymerization in IK cells, as blockade of ERK1/2 phosphorylation reversed AnxA1-induced Muc-1 and claudin-1 expression. Moreover, FPR2 activation by AnxA1 induced vascular endothelial growth factor (VEGF) secretion by IK cells, and the supernatant of AnxA1-treated IK cells evoked angiogenesis in vitro. In conclusion, these data highlight the role of the AnxA1/FPR1/FPR2 pathway in uterine epithelial control of blastocyst implantation.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Útero / Blastocisto / Anexina A1 / Receptores de Formil Peptídeo Limite: Animals / Female / Humans Idioma: En Revista: Cells Ano de publicação: 2020 Tipo de documento: Article País de afiliação: Brasil País de publicação: Suíça

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Útero / Blastocisto / Anexina A1 / Receptores de Formil Peptídeo Limite: Animals / Female / Humans Idioma: En Revista: Cells Ano de publicação: 2020 Tipo de documento: Article País de afiliação: Brasil País de publicação: Suíça