BioProject

Microglia are the supervisors maintaining intracerebral homeostasis, which function importantly in determining the outcome of ischemic stroke. More...

Microglia are the supervisors maintaining intracerebral homeostasis, which function importantly in determining the outcome of ischemic stroke. Plxdc2 is a single-transmembrane protein and mainly studied in the development of central nervous system and cancers, whereas its role in the function of microglia remains elusive. In this study, based on our previous scRNA-seq of ischemic brain and transcriptomic analysis of the isolated microglia from ischemic brain, we found that Plxdc2 was abundantly expressed in microglia and remarkably downregulated after stroke. Further, with adeno-associated virus (AAV) overexpressing or lentivirus interfering Plxdc2 in microglia in vivo, Plxdc2 was proved to protect against ischemic brain injury. Plxdc2 helps maintain microglial homeostatic state both in vitro and in vivo, and downregulation of Plxdc2 exacerbated microglial inflammatory response in ischemic stroke. In addition, we found that Plxdc2 participated in governing the activation of NF-kB p65 signaling, and also modulated microglial lipid metabolism. Mechanistically, Plxdc2 was found to facilitate the activation of PPARy, which might account for its impact on NF-kB p65 signaling and lipid metabolism in microglia. Overall, our results illustrated a vital role of Plxdc2 in modulating post-stroke microglial activation, which holds potential to be a novel target for immunomodulation in ischemic stroke. Less...