Back to Search
Start Over
USP14 deficiency inhibits neointima formation following vascular injury via degradation of Skp2 protein
- Source :
- Cell Death Discovery, Vol 10, Iss 1, Pp 1-13 (2024)
- Publication Year :
- 2024
- Publisher :
- Nature Publishing Group, 2024.
-
Abstract
- Abstract Ubiquitin-proteasome system (UPS) is involved in vascular smooth muscle cell (VSMC) proliferation. Deubiquitinating enzymes (DUBs) have an essential role in the UPS-regulated stability of the substrate; however, the function of DUBs in intimal hyperplasia remains unclear. We screened DUBs to identify a protein responsible for regulating VSMC proliferation and identified USP14 protein that mediates cancer development, inflammation, and foam cell formation. USP14 promotes human aortic smooth muscle cell and A7r5 cell growth in vitro, and its inhibition or deficiency decreases the intimal area in the mice carotid artery ligation model. In addition, USP14 stabilizes Skp2 expression by decreasing its degradation, while Skp2 overexpression rescues USP14 loss-induced issues. The current findings suggested an essential role of USP14 in the pathology of vascular remodeling, deeming it a promising target for arterial restenosis therapy.
Details
- Language :
- English
- ISSN :
- 20587716
- Volume :
- 10
- Issue :
- 1
- Database :
- Directory of Open Access Journals
- Journal :
- Cell Death Discovery
- Publication Type :
- Academic Journal
- Accession number :
- edsdoj.3cc33382f30a4b23ad5add0c831d0a1d
- Document Type :
- article
- Full Text :
- https://doi.org/10.1038/s41420-024-02069-1