Prostacyclin receptor up-regulates the expression of angiogenic genes in human endometrium via cross talk with epidermal growth factor receptor and the extracellular signaling receptor kinase 1/2 pathway

被引:24
|
作者
Smith, OPM
Battersby, S
Sales, KJ
Critchley, HOD
Jabbour, HN
机构
[1] MRC, Human Reprod Sci Unit, Ctr Reprod Biol, Queens Med Res Inst, Edinburgh EH16 4TJ, Midlothian, Scotland
[2] Univ Edinburgh, Dept Reprod & Dev Sci, Ctr Reprod Biol, Queens Med Res Inst, Edinburgh EH16 4TJ, Midlothian, Scotland
基金
英国医学研究理事会;
关键词
D O I
10.1210/en.2005-1073
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Prostacyclin (PGI) is a member of the prostanoid family of lipid mediators that mediates its effects through a seven-transmembrane G protein-coupled receptor (IP receptor). Recent studies have ascertained a role for prostanoid-receptor signaling in angiogenesis. In this study we examined the temporal-spatial expression of the IP receptor within normal human endometrium and additionally explored the signaling pathways mediating the role of IP receptor in activation of target angiogenic genes. Quantitative RT-PCR analysis demonstrated the highest endometrial expression of the IP receptor during the menstrual phase compared with all other stages of the menstrual cycle. Immunohistochemical analysis localized the site of IP receptor expression to the glandular epithelial compartment with stromal and perivascular cell immunoreactivity. Expression of the immunoreactive IP receptor protein was greatest during the proliferative and early secretory phases of the menstrual cycle. To explore the role of the IP receptor in glandular epithelial cells, we used the Ishikawa endometrial epithelial cell line. Stimulation of Ishikawa cells and human endometrial biopsy explants with 100 nM iloprost (a PGI analog) rapidly activated ERK1/2 signaling and induced the expression of proangiogenic genes, basic fibroblast growth factor, angiopoietin-1, and angiopoietin-2, in an epidermal growth factor receptor (EGFR)-dependent manner. Furthermore, EGFR colocalized with IP receptor in the glandular epithelial compartment. These data suggest that PGI-IP interaction within glandular epithelial cells can promote the expression of proangiogenic genes in human endometrium via cross talk with the EGFR.
引用
收藏
页码:1697 / 1705
页数:9
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