GSE141972 TGF β-activated kinase 1-dependent microglial and macrophage responses aggravate long-term outcomes after ischemic stroke

Contributors : Yejie Shi ; Jun ChenSeries Type : Expression profiling by high throughput sequencingOrganism : Mus musculusMicroglia/macrophages (Mi/M Φ) can profoundly influence stroke outcomes by acquiring functionally dominant phenotypes (pro-inflammatory or anti-inflammatory; neurotoxic or neuroprotective). Identification of the molecular mechanisms that dictate the functional status of Mi/MΦ after brain ischemia/reperfusion may reveal novel therapeutic targets for stroke. We hypothesized that activation of TGFβ-activated kinase 1 (TAK1), a key MAP3K upstream of multiple inflammation-regulating pathways, drives Mi/MΦ towards a pro-inflammatory phenotype and potentiates ischemia/reperfusion brain injury. Young adult mice were subjecte d to 1 h of middle cerebral artery occlusion (MCAO) followed by reperfusion. TAK1 was targeted by tamoxifen-induced Mi/MΦ-specific knockout (mKO). Mi/MΦ functional status and brain inflammatory profiles were assessed 3 days after MCAO by RNA-seq of flow cytometry-sorted brain Mi/MΦ. The results showed that TAK1 promotes ischemia/reperfusion-induced inflammation, brain injury, and maladaptive behavior by enhancing pro-inflammatory and neurotoxic Mi/MΦ responses.
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Mus musculus Source Type: research