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Regulation of miR-101/miR-199a-3p by the epithelial sodium channel during embryo implantation: involvement of CREB phosphorylation
- Source :
- Reproduction (Cambridge, England). 148(6)
- Publication Year :
- 2014
-
Abstract
- In our previous study, we have demonstrated that the epithelial sodium channel (ENaC) mediates the embryo-derived signals leading to the activation of CREB and upregulation of cyclooxygenase type 2 (COX2) required for embryo implantation. This study aims to investigate whether microRNAs (miRNAs) are involved in the ENaC-induced upregulation of COX2 during embryo implantation. The results show that the levels of miR-101 and miR-199a-3p, two COX2 targeting miRNAs, are reduced by ENaC activation, and increased by ENaC inhibition or knock-down of ENaC subunit (ENaCĪ±) in human endometrial surface epithelial (HES) cells or in mouse uteri during implantation. Phosphorylation of CREB is induced by the activation of ENaC, and blocked by ENaC inhibition or knockdown in HES cells. Knockdown of ENaCĪ± or CREB in HES cells or in mouse uterusin vivoresults in increases in miR-101 and miR-199a-3p, accompanied with decreases in COX2 protein levels and reduction in implantation rate. The downregulation of COX2 caused by knockdown of ENaC or CREB can be recovered by the inhibitors of miR-101 or miR-199a-3p in HES cells. These results reveal a novel molecular mechanism modulating COX2 expression during embryo implantation via ENaC-dependent CREB activation and COX2-targeting miRNAs.
- Subjects :
- Epithelial sodium channel
Embryology
macromolecular substances
In Vitro Techniques
CREB
Endometrium
Mice
Endocrinology
Downregulation and upregulation
microRNA
Animals
Humans
Embryo Implantation
Phosphorylation
RNA, Small Interfering
Cyclic AMP Response Element-Binding Protein
Epithelial Sodium Channels
Cells, Cultured
Gene knockdown
Mice, Inbred ICR
biology
urogenital system
Chemistry
food and beverages
Obstetrics and Gynecology
Embryo
Epithelial Cells
Cell Biology
respiratory system
Embryo, Mammalian
MicroRNAs
Reproductive Medicine
Cyclooxygenase 2
Models, Animal
biology.protein
Cancer research
Female
Cyclooxygenase
hormones, hormone substitutes, and hormone antagonists
Signal Transduction
Subjects
Details
- ISSN :
- 17417899
- Volume :
- 148
- Issue :
- 6
- Database :
- OpenAIRE
- Journal :
- Reproduction (Cambridge, England)
- Accession number :
- edsair.doi.dedup.....489aa9e156cc0c0635c1d6e8fedc54d3