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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Aug 30, 2023 |
| Title |
CD44 connects autophagy decline and aging in the vascular endothelium |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
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 aging 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 aging vascular endothelium and Caenorhabditis elegans, respectively, suggesting that an age-dependent increase in CD44 induces autophagy decline and aging 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 aging characteristics associated with decreased basal autophagy. Autophagy activation suppresses the premature aging 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 aging.
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| Overall design |
We knock-down CD44 in HUVECs by siRNA (S1, S2). We then analyzed the differentially expressed autophagy related genes compared with control (SC) using the Affymetrix Human GeneChip® Gene1.0 ST platform. Array data was processed by Affymetrix Exon Array Computational Tool. No techinical replicates were performed.
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| Contributor(s) |
Zhang L, Yang P |
| Citation(s) |
37684253 |
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| Submission date |
Jul 05, 2023 |
| Last update date |
Sep 21, 2023 |
| Contact name |
Lu Zhang |
| E-mail(s) |
zhanglu@haut.edu.cn
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| Organization name |
Henan University of Technology
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| Street address |
Henan University of Technology, Lianhua Street, Zhengzhou
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| City |
Zhengzhou |
| State/province |
Henan |
| ZIP/Postal code |
450001 |
| Country |
China |
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| Platforms (1) |
| GPL17586 |
[HTA-2_0] Affymetrix Human Transcriptome Array 2.0 [transcript (gene) version] |
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| Samples (3) |
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| Relations |
| BioProject |
PRJNA991525 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE236523_Processed_data.xlsx |
19.0 Mb |
(ftp)(http) |
XLSX |
| GSE236523_RAW.tar |
75.1 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
| Processed data are available on Series record |
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