Nucleoporin93 limits Yap activity to prevent endothelial cell senescence

• DOI: 10.1111/acel.14095
• Publication Date: 2024-02-13T10:00:01Z
• Authors: Tung D. Nguyen; Mihir K. Rao; Shaiva P. Dhyani; Justin M. Banks; Michael A. Winek; Julia Michalkiewicz; Monica Y. Lee
• Keywords: Senescence; Endothelial Dysfunction

Abstract As the innermost lining of vasculature, endothelial cells (ECs) are constantly subjected to systemic inflammation and particularly vulnerable aging. Endothelial health is hence vital prevent age‐related vascular disease. Healthy ECs rely on proper localization transcription factors via nuclear pore complexes (NPCs) govern cellular behavior. Emerging studies report NPC degradation with natural aging, suggesting impaired nucleocytoplasmic transport in age‐associated EC dysfunction. We herein identify nucleoporin93 (Nup93), a crucial structural protein, as an indispensable player protection. Nup93 protein levels significantly reduced vasculature aged mice, paralleling observations loss when using vitro models senescence. The human induces cell senescence promotes expression inflammatory adhesion molecules, where restoring senescent reverses features Mechanistically, we find that both impair transport, leading accumulation Yap downstream inflammation. Pharmacological indicate hyperactivation primary consequence ECs. Collectively, our findings maintenance key determinant health, aging targets function novel mechanism