USP10 exacerbates neointima formation by stabilizing Skp2 protein in vascular smooth muscle cells.

The underlying mechanism of neointima formation remains unclear. Ubiquitin-specific peptidase 10 (USP10) is a deubiquitinase that plays a major role in cancer development and progression. However, the function of USP10 in arterial restenosis is unknown. Herein, USP10 expression was detected in mouse arteries and increased after carotid ligation. The inhibition of USP10 exhibited thinner neointima in the model of mouse carotid ligation. In vitro data showed that USP10 deficiency reduced proliferation and migration of rat thoracic aorta smooth muscle cells (A7r5) and human aortic smooth muscle cells (HASMCs). Mechanically, USP10 can bind to Skp2 and stabilize its protein level by removing polyubiquitin on Skp2 in the cytoplasm. The overexpression of Skp2 abrogated cell cycle arrest induced by USP10 inhibition. Overall, the current study demonstrated that USP10 is involved in vascular remodeling by directly promoting VSMC proliferation and migration via stabilization of Skp2 protein expression. Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.

Citation

Xiaohong Xia, Xiaolin Liu, Renjie Chai, Qiong Xu, Zhenyu Luo, Jielei Gu, Yangshuo Jin, Tumei Hu, Cuifu Yu, Bijun Du, Hongbiao Huang, Wenchao Ou, Shiming Liu, Ningning Liu. USP10 exacerbates neointima formation by stabilizing Skp2 protein in vascular smooth muscle cells. The Journal of biological chemistry. 2021 Nov;297(5):101258

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PMID: 34599966

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