Regional and Cell-Type-Specific Activation of YAP/TAZ Underlies Glial Responses in LPS-Induced Neuroinflammation.

Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ), core effectors of the Hippo pathway, are emerging as mechanosensitive regulators of inflammation and tissue repair. However, their roles in neuroinflammation remain poorly understood. Here, we investigated the spatial and temporal expression of YAP/TAZ in glial cells under lipopolysaccharide (LPS)-induced neuroinflammation in mice. Immunofluorescence revealed selective upregulation and nuclear translocation of YAP/TAZ in astrocytes within the spinal cord and specific brain regions following LPS injection, while microglial expression remained negligible. To further elucidate YAP/TAZ-related molecular responses, we performed RNA-sequencing of spinal cord tissue on Day 3 post-LPS injection. Transcriptomic analysis revealed significant upregulation of glial activation markers (Aif1, Tmem119, Vim) and YAP/TAZ-associated genes involved in mechanosensation (Piezo1), inflammasome signaling (Nlrp3), and immune cell adhesion (Icam1, Vcam1). These results suggest that YAP/TAZ may integrate mechanical and immune-inflammatory cues in astrocytes and contribute to glial activation and neurovascular modulation under inflammatory conditions. Our study highlights the context-dependent role of YAP/TAZ in central nervous system inflammation and underscores their potential as therapeutic targets in neuroinflammatory diseases.