Lu Zhang, Peichang Yang, Jingxuan Chen, Zhiqiang Chen, Zhihui Liu, Gaoqing Feng, Fangfang Sha, Zirui Li, Zaoyi Xu, Yating Huang, Xiaotong Shi, Xuebiao Li, Jiatian Cui, Chenyi Zhang, Pei Fan, Liuqing Cui, Yunpeng Shen, Guangzhou Zhou, Hongjuan Jing, Shiwei Ma
The decline of endothelial autophagy is closely related to vascular senescence and disease, although the molecular mechanisms connecting these outcomes in vascular endothelial cells (VECs) remain unclear. Here, we identify a crucial role for CD44, a multifunctional adhesion molecule, in controlling autophagy and ageing in VECs. The CD44 intercellular domain (CD44ICD) negatively regulates autophagy by reducing PIK3R4 and PIK3C3 levels and disrupting STAT3-dependent PtdIns3K complexes. CD44 and its homologue clec-31 are increased in ageing vascular endothelium and Caenorhabditis elegans, respectively, suggesting that an age-dependent increase in CD44 induces autophagy decline and ageing phenotypes...
September 8, 2023: Nature Communications