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bioRxiv · 10.1101/2024.07.17.603777

PATJ regulates cell stress responses and vascular remodeling post-stroke

Zhang, M.·Jiang, W.·Arkelius, K.·Swanson, R. A.·Ma, D. K.·Singhal, N. S.
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Abstract

PALS1-associated tight junction (PATJ) protein is linked to metabolic disease and stroke in human genetic studies. Despite the recognized role of PATJ in cell polarization, its specific functions in metabolic disease and ischemic stroke recovery remain largely unexplored. Using a mouse model of stroke, we found post-ischemic stroke duration-dependent increase of PATJ abundance in endothelial cells. PATJ knock-out (KO) HEK293 cells generated by CRISPR-Cas9 suggest roles for PATJ in cell proliferation, migration, mitochondrial stress response, and interactions with the Yes-associated protein (YAP)-1 signaling pathway. Notably, PATJ deletion altered YAP1 nuclear translocation. PATJ KO cells demonstrated extensive transcriptional reprograming based on RNA sequencing analysis. Crucially, we identified dysregulation in genes central to vascular development, stress response, and metabolism, including RUNX1, HEY1, NUPR1, and HK2. These insights offer a new understanding of PATJs complex regulatory functions within cellular and vascular physiology and help lay the groundwork for therapeutic strategies targeting endothelial PATJ-mediated pathways for stroke rehabilitation and neurovascular repair.

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Zhang, M., Jiang, W., Arkelius, K., Swanson, R. A., Ma, D. K., Singhal, N. S.. 2024-07-22. PATJ regulates cell stress responses and vascular remodeling post-stroke. https://doi.org/10.1101/2024.07.17.603777

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