Details
- Autor(en) / Beteiligte
- Titel
- Annexin A1/Formyl Peptide Receptor Pathway Controls Uterine Receptivity to the Blastocyst
- Ist Teil von
- Cells (Basel, Switzerland), 2020-05, Vol.9 (5), p.1188
- Ort / Verlag
- Switzerland: MDPI AG
- Erscheinungsjahr
- 2020
- Link zum Volltext
- Quelle
- Free E-Journal (出版社公開部分のみ）
- Beschreibungen/Notizen
- 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 , 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.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 2073-4409eISSN: 2073-4409DOI: 10.3390/cells9051188Titel-ID: cdi_doaj_primary_oai_doaj_org_article_7aaf098a691d4cf4bb407e22d197d61d
- Format
- –
- Schlagworte
- Actin, Actins - metabolism, Angiogenesis, Animals, Annexin A1 - metabolism, Antibiotics, Antibodies, Blastocyst - metabolism, Cell Line, claudin-1, Claudin-1 - metabolism, Cytokines, Embryo Implantation, Epithelial cells, Epithelial Cells - metabolism, ERK1/2 pathway, Extracellular signal-regulated kinase, F-actin polymerization, Female, Flow cytometry, Formyl peptide receptors, Human Umbilical Vein Endothelial Cells - metabolism, Humans, Inflammation, Interleukin 6, Kinases, Life sciences, MAP Kinase Signaling System, Mice, Inbred C57BL, Mucin, mucin-1, Mucin-1 - metabolism, Neovascularization, Physiologic, Peptides, Phosphorylation, Physiology, Polymerization, Proteins, Receptors, Formyl Peptide - metabolism, Spheroids, Spheroids, Cellular - cytology, Spheroids, Cellular - metabolism, Trophoblasts - cytology, Trophoblasts - metabolism, Uterus, Uterus - physiology, Vascular endothelial growth factor, Vascular Endothelial Growth Factor A - metabolism, zona occludens, Zonula Occludens-1 Protein - metabolism