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Publication : Upregulation of Microglial ZEB1 Ameliorates Brain Damage after Acute Ischemic Stroke.

First Author  Li D Year  2018
Journal  Cell Rep Volume  22
Issue  13 Pages  3574-3586
PubMed ID  29590624 Mgi Jnum  J:270727
Mgi Id  MGI:6278666 Doi  10.1016/j.celrep.2018.03.011
Citation  Li D, et al. (2018) Upregulation of Microglial ZEB1 Ameliorates Brain Damage after Acute Ischemic Stroke. Cell Rep 22(13):3574-3586
abstractText  Microglia are a key immune-competent cell type that respond to environmental and physiological changes during ischemic stroke. However, the molecular mechanisms controlling post-ischemic microglia activity are unclear. Understanding these mechanisms may ultimately reduce disease burden and allow the manipulation of microglia responses to shape the outcomes of stroke. Here, we report that, after experimentally induced stroke, ZEB1 is highly expressed in ipsilateral cerebral hemisphere, where it is upregulated mainly in microglia. Using a conditional transgenic mouse, we found that ZEB1 upregulation in microglia regulates immune responses in the CNS and alleviates brain injury after ischemic stroke. Our data indicate that ZEB1 overexpression mediates microglia responses and, in turn, inhibits the production of astrocytic CXCL1 through the TGF-beta1-dependent pathway. Reduced CXCL1 leads to a decline in neutrophil infiltration into the brain, thereby reducing CNS inflammation. Our results demonstrate the importance of ZEB1 in microglia-orchestrated neuroinflammation and suggest a potential means for reducing stroke-induced neurological injury.
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