Annexin A1/Formyl Peptide Receptor Pathway Controls Uterine Receptivity to the Blastocyst

Autor(es)

Hebeda, Cristina B. ^[1] ; Sandri, Silvana ^[1] ; Benis, Claudia M. ^[1] ; de Paula-Silva, Marina ^[1] ; Loiola, Rodrigo A. ^[1] ; Reutelingsperger, Chris ^[2] ; Perretti, Mauro ^[3] ; Farsky, Sandra H. P. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Sch Pharmaceut Sci, Dept Clin & Toxicol Anal, BR-05508000 Sao Paulo - Brazil

^[2] Maastricht Univ, Med Ctr, Fac Hlth Med & Life Sci, NL-6211 LK Maastricht - Netherlands

^[3] Queen Mary Univ London, William Harvey Res Inst, London EC1M 6BQ - England

• Tipo de documento: Artigo Científico
• Fonte: CELLS; v. 9, n. 5 MAY 2020.
• Citações Web of Science: 0

Resumo

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. (AU)

• Processo FAPESP: 14/07328-4 - Identificação de vias endógenas para o controle da inflamação
• Beneficiário: Sandra Helena Poliselli Farsky
• Modalidade de apoio: Auxílio à Pesquisa - Temático