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CD44 connects autophagy decline and ageing in the vascular endothelium.
Zhang, Lu; Yang, Peichang; Chen, Jingxuan; Chen, Zhiqiang; Liu, Zhihui; Feng, Gaoqing; Sha, Fangfang; Li, Zirui; Xu, Zaoyi; Huang, Yating; Shi, Xiaotong; Li, Xuebiao; Cui, Jiatian; Zhang, Chenyi; Fan, Pei; Cui, Liuqing; Shen, Yunpeng; Zhou, Guangzhou; Jing, Hongjuan; Ma, Shiwei.
Afiliación
  • Zhang L; College of Bioengineering, Henan University of Technology, Lianhua Street, Zhengzhou, 450001, China. zhanglu@haut.edu.cn.
  • Yang P; College of Bioengineering, Henan University of Technology, Lianhua Street, Zhengzhou, 450001, China.
  • Chen J; College of Bioengineering, Henan University of Technology, Lianhua Street, Zhengzhou, 450001, China.
  • Chen Z; College of Bioengineering, Henan University of Technology, Lianhua Street, Zhengzhou, 450001, China.
  • Liu Z; College of Bioengineering, Henan University of Technology, Lianhua Street, Zhengzhou, 450001, China.
  • Feng G; College of Bioengineering, Henan University of Technology, Lianhua Street, Zhengzhou, 450001, China.
  • Sha F; College of Bioengineering, Henan University of Technology, Lianhua Street, Zhengzhou, 450001, China.
  • Li Z; College of Bioengineering, Henan University of Technology, Lianhua Street, Zhengzhou, 450001, China.
  • Xu Z; College of Bioengineering, Henan University of Technology, Lianhua Street, Zhengzhou, 450001, China.
  • Huang Y; College of Bioengineering, Henan University of Technology, Lianhua Street, Zhengzhou, 450001, China.
  • Shi X; College of Bioengineering, Henan University of Technology, Lianhua Street, Zhengzhou, 450001, China.
  • Li X; College of Bioengineering, Henan University of Technology, Lianhua Street, Zhengzhou, 450001, China.
  • Cui J; College of Bioengineering, Henan University of Technology, Lianhua Street, Zhengzhou, 450001, China.
  • Zhang C; College of Bioengineering, Henan University of Technology, Lianhua Street, Zhengzhou, 450001, China.
  • Fan P; College of Bioengineering, Henan University of Technology, Lianhua Street, Zhengzhou, 450001, China.
  • Cui L; College of Bioengineering, Henan University of Technology, Lianhua Street, Zhengzhou, 450001, China.
  • Shen Y; College of Bioengineering, Henan University of Technology, Lianhua Street, Zhengzhou, 450001, China.
  • Zhou G; College of Bioengineering, Henan University of Technology, Lianhua Street, Zhengzhou, 450001, China.
  • Jing H; College of Bioengineering, Henan University of Technology, Lianhua Street, Zhengzhou, 450001, China.
  • Ma S; College of Bioengineering, Henan University of Technology, Lianhua Street, Zhengzhou, 450001, China.
Nat Commun ; 14(1): 5524, 2023 09 08.
Article en En | MEDLINE | ID: mdl-37684253
ABSTRACT
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. Accordingly, CD44 knockdown ameliorates age-associated phenotypes in VECs. The endothelium-specific CD44ICD knock-in mouse is shorter-lived, with VECs exhibiting obvious premature ageing characteristics associated with decreased basal autophagy. Autophagy activation suppresses the premature ageing of human and mouse VECs overexpressing CD44ICD, function conserved in the CD44 homologue clec-31 in C. elegans. Our work describes a mechanism coordinated by CD44 function bridging autophagy decline and ageing.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Endotelio Vascular / Envejecimiento Prematuro Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2023 Tipo del documento: Article País de afiliación: China
Texto completo
Añadir a Mi BVS
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XML
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Endotelio Vascular / Envejecimiento Prematuro Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2023 Tipo del documento: Article País de afiliación: China