PreImplantation factor promotes neuroprotection by targeting microRNA let-7 (original) (raw)
ADS
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- Zhou, Jichun ;
- Yang, Lihua ;
- Gao, Yuan ;
- Wu, Fuju ;
- Schoeberlein, Andreina ;
- Surbek, Daniel ;
- Barnea, Eytan R. ;
- Paidas, Michael ;
- Huang, Yingqun
Abstract
Secreted from viable embryos into the maternal circulation, PreImplantation factor (PIF) has long been implicated in modulating maternal immune tolerance and promoting embryo implantation. Recent evidence also suggests its possible therapeutic use in CNS disorders. However, the molecular signal-transduction pathways driving PIF-mediated effects are unclear. Using murine cell culture combined with a rat hypoxic-ischemic brain injury model, we show that synthetic PIF (sPIF) inhibits microRNA let-7 biogenesis by destabilizing the key microRNA-processing protein, KH-type splicing regulatory protein, in a Toll-like receptor 4-dependent manner. This regulation, together with its induced upregulation of the anti-inflammatory cytokine IL-10, may contribute to sPIF-mediated neuroprotection in vivo and also may underlie PIF's physiological role in maternal immune modulation and embryo implantation.
Publication:
Proceedings of the National Academy of Science
Pub Date:
September 2014
DOI:
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