Ming Jiang

The WRKY gene family is among the largest families of transcription factors (TFs) in higher plants. By regulating the plant hormone signal transduction pathway, these TFs play critical roles in some plant processes in response to biotic and abiotic stress. Various bodies of research have demonstrated the important biological functions of WRKY TFs in plant response to different kinds of biotic and abiotic stresses and working mechanisms. However, very little summarization has been done to review their research progress. Not just important TFs function in plant response to biotic and abiotic stresses, WRKY also participates in carbohydrate synthesis, senescence, development, and secondary metabolites synthesis. WRKY proteins can bind to W-box (TGACC (A/T)) in the promoter of its target genes and activate or repress the expression of downstream genes to regulate their stress response. Moreover, WRKY proteins can interact with other TFs to regulate plant defensive responses. In the present review, we focus on the structural characteristics of WRKY TFs and the research progress on their functions in plant responses to a variety of stresses.

AIMS: Blood-borne monocytes/macrophages infiltrate the brain in massive numbers after ischemic stroke, but their impact on poststroke brain injury and recovery remains elusive. This study examined the transcriptomic changes in monocytes/macrophages after ischemic stroke and the functional implications of these changes, particularly with regards to the contribution of these cells to the phagocytic clearance of dead/dying cells (efferocytosis) in the poststroke brain. METHODS: We performed whole-genome RNA sequencing on the monocyte/macrophage population sorted from mouse brain and peripheral blood 5 days after permanent focal cerebral ischemia. In addition, the spatial and temporal profiles of macrophage efferocytosis were examined in vivo by immunohistochemistry 3-7 days after brain ischemia. RESULTS: Robust transcriptomic changes occurred in monocytes/macrophages upon infiltrating the poststroke brain. Functional enrichment analysis revealed a transcriptome of brain macrophages that strongly favored efferocytic activity. A large number of efferocytosis-related genes were upregulated in brain macrophages, the products of which are essential components involved in various steps of efferocytosis, such as chemotaxis, recognition of dead cells, engulfment, and processing of phagosomes. The efferocytic activity of brain macrophages were verified by immunohistochemistry, wherein Iba1-labeled microglia/macrophages effectively cleared apoptotic neurons in the infarct during the subacute stage after brain ischemia. We also identified PPARγ and STAT6 as potential upstream regulators that shaped this proefferocytic and inflammation-resolving transcriptome of macrophages in the poststroke brain. CONCLUSION: Macrophages play a crucial role in the phagocytic clearance of dead neurons after ischemic stroke and promote the resolution of inflammation in the brain. Molecular therapies that enhance macrophage efferocytic capability may be promising treatments for ischemic stroke by facilitating inflammation resolution, brain repair, and recovery of neurological functions.

Background and Purpose— Microglia/macrophages (Mi/MΦ) can profoundly influence stroke outcomes by acquiring functionally dominant phenotypes (proinflammatory or anti-inflammatory; deleterious or salutary). 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 TAK1 (transforming growth factor beta-activated kinase 1), a key MAP3K upstream of multiple inflammation-regulating pathways, drives Mi/MΦ toward a proinflammatory phenotype and potentiates ischemia/reperfusion brain injury. Methods— Young adult mice were subjected to 1 hour of middle cerebral artery occlusion (MCAO) followed by reperfusion. TAK1 was targeted by tamoxifen-induced Mi/MΦ-specific knockout or administration of a selective inhibitor 5Z-7-Oxozeaenol after MCAO. Neurobehavioral deficits and long-term gray matter and white matter injury were assessed up to 35 days after MCAO. Mi/MΦ functional status and brain inflammatory profiles were assessed 3 days after MCAO by RNA-seq, flow cytometry, and immunohistochemistry. Results— TAK1 Mi/MΦ-specific knockout markedly ameliorated neurological deficits in the rotarod and cylinder tests for at least 35 days after MCAO. Mechanistically, RNA-seq of purified brain Mi/MΦ demonstrated that proinflammatory genes and their predicted biological functions were downregulated or inhibited in microglia and macrophages from TAK1 Mi/MΦ-specific knockout mice versus WT mice 3 days after MCAO. Consistent with the anti-inflammatory phenotype of Mi/MΦ-specific knockout, oxozeaenol treatment mitigated neuroinflammation 3 days after MCAO, manifested by less Iba1 + /CD16 + proinflammatory Mi/MΦ and suppressed brain invasion of various peripheral immune cells. Oxozeaenol treatment beginning 2 hours after MCAO improved long-term sensorimotor and cognitive functions in the foot fault, rotarod, and water maze tests. Furthermore, Oxozeaenol promoted both gray matter and white matter integrity 35 days after MCAO. Conclusions— TAK1 promotes ischemia/reperfusion-induced inflammation, brain injury, and maladaptive behavior by enhancing proinflammatory and deleterious Mi/MΦ responses. Therefore, TAK1 inhibition is a promising therapy to improve long-term stroke outcomes.