USP14 deficiency inhibits neointima formation following vascular injury via degradation of Skp2 protein

Autor: Xiaohong Xia, Xiaolin Liu, Qiong Xu, Jielei Gu, Sisi Ling, Yajing Liu, Rongxue Li, Min Zou, Siqin Jiang, Zhiwei Gao, Canshan Chen, Shiming Liu, Ningning Liu
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: Cell Death Discovery, Vol 10, Iss 1, Pp 1-13 (2024)
Druh dokumentu: article
ISSN: 2058-7716
DOI: 10.1038/s41420-024-02069-1
Popis: 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.
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