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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Gao, Yuan Huang, Yingqun Mueller, Martin Barnea, Eytan R. Wu, Fuju Zhou, Jichun Yang, Lihua Schoeberlein, Andreina Surbek, Daniel Paidas, Michael |
| Description | Author Affiliation: Mueller M ( Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale University School of Medicine, New Haven, CT 06510); Zhou J ( Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale University School of Medicine, New Haven, CT 06510); Yang L ( Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale University School of Medicine, New Haven, CT 06510); Gao Y ( Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale University School of Medicine, New Haven, CT 06510); Wu F ( Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale University School of Medicine, New Haven, CT 06510); Schoeberlein A ( Department of Clinical Research, University of Bern, 3012 Bern, Switzerland); Surbek D ( Department of Obstetrics and Gynecology, University Hospital, 3010 Bern, Switzerland); Barnea ER ( Society for the Investigation of Early Pregnancy, Cherry Hill, NJ 08003); Paidas M ( Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale University School of Medicine, New Haven, CT 06510); Huang Y ( Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale University School of Medicine, New Haven, CT 06510); |
| Abstract | Dysfunction and loss of neurons are the major characteristics of CNS disorders that include stroke, multiple sclerosis, and Alzheimer's disease. Activation of the Toll-like receptor 7 by extracellular microRNA let-7, a highly expressed microRNA in the CNS, induces neuronal cell death. Let-7 released from injured neurons and immune cells acts on neighboring cells, exacerbating CNS damage. Here we show that a synthetic peptide analogous to the mammalian PreImplantation factor (PIF) secreted by developing embryos and which is present in the maternal circulation during pregnancy inhibits the biogenesis of let-7 in both neuronal and immune cells of the mouse. The synthetic peptide, sPIF, destabilizes KH-type splicing regulatory protein (KSRP), a key microRNA-processing protein, in a Toll-like receptor 4 (TLR4)-dependent manner, leading to decreased production of let-7. Furthermore, s.c. administration of sPIF into neonatal rats following hypoxic-ischemic brain injury robustly rescued cortical volume and number of neurons and decreased the detrimental glial response, as is consistent with diminished levels of KSRP and let-7 in sPIF-treated brains. Our results reveal a previously unexpected mechanism of action of PIF and underscore the potential clinical utility of sPIF in treating hypoxic-ischemic brain damage. The newly identified PIF/TLR4/KSRP/let-7 regulatory axis also may operate during embryo implantation and development. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 38 |
| Volume Number | 111 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 2014-09-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Blastocyst Metabolism Embryo Implantation Physiology MicroRNAs Peptides Animals Cytology Brain Ischemia Genetics Mice Pregnancy RNA-Binding Proteins Rats, Wistar Toll-Like Receptor 4 Trans-Activators Research Support, Non-U.S. Gov't Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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