Aging-regulated PNUTS maintains endothelial barrier function via SEMA3B suppression

Noelia Lozano-Vidal
Amsterdam UMC
May 7, 2024
Mol Cancer Ther
https://pubmed.ncbi.nlm.nih.gov/38714838

This article is currently being updated. View its version on PubMed.

https://pubmed.ncbi.nlm.nih.gov/38714838

Research summary

This study investigates the role of Phosphatase 1 Nuclear Targeting Subunit (PNUTS) in endothelial cell aging and its impact on endothelial barrier function. The research explores how PNUTS expression influences the expression of semaphorin 3B (SEMA3B) and the subsequent effects on vascular integrity during aging.

Key outcome of the study

Loss of PNUTS in endothelial cells led to increased expression of SEMA3B, resulting in compromised endothelial barrier function and vascular leakage. Silencing SEMA3B restored barrier integrity, highlighting the critical role of the PNUTS-SEMA3B axis in maintaining vascular homeostasis during aging.

Model

The study utilized an endothelial-specific inducible PNUTS-deficient mouse model, referred to as PNUTSEC-KO, developed in collaboration with genOway. This model allows for the temporal and spatial deletion of the PNUTS gene specifically in endothelial cells, enabling the assessment of PNUTS function in vascular biology.

TARGET:
Ppp1r10
PNUTS, CAT 53, FB19

Keywords

Cardiovascular diseases, Endothelial dysfunction, Vascular aging, Barrier integrity, Angiogenesis

Technical specifications

Endothelial-specific inducible Knockout, Cre-loxP system, Temporal gene deletion, Vascular leakage assessment, Gene expression analysis

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