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

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

doi:10.1016/j.jbc.2021.101258

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

J Biol Chem. 2021 Nov;297(5):101258. doi: 10.1016/j.jbc.2021.101258. Epub 2021 Sep 29.

Authors

Xiaohong Xia¹, Xiaolin Liu², Renjie Chai², Qiong Xu², Zhenyu Luo², Jielei Gu², Yangshuo Jin², Tumei Hu³, Cuifu Yu³, Bijun Du⁴, Hongbiao Huang³, Wenchao Ou², Shiming Liu⁵, Ningning Liu⁶

Affiliations

¹ Guangdong Key Laboratory of Vascular Diseases, State Key Laboratory of Respiratory Disease, Guangzhou Institute of Cardiovascular Disease, The Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, China; Guangzhou Municipal and Guangdong Provincial Key Laboratory of Protein Modification and Degradation, School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou, China.
² Guangdong Key Laboratory of Vascular Diseases, State Key Laboratory of Respiratory Disease, Guangzhou Institute of Cardiovascular Disease, The Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, China.
³ Guangzhou Municipal and Guangdong Provincial Key Laboratory of Protein Modification and Degradation, School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou, China.
⁴ Department of Obstetrics, The Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, China.
⁵ Guangdong Key Laboratory of Vascular Diseases, State Key Laboratory of Respiratory Disease, Guangzhou Institute of Cardiovascular Disease, The Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, China. Electronic address: liushiming@gzhmu.edu.cn.
⁶ Guangdong Key Laboratory of Vascular Diseases, State Key Laboratory of Respiratory Disease, Guangzhou Institute of Cardiovascular Disease, The Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, China. Electronic address: liuningning@gzhmu.edu.cn.

Abstract

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.

Keywords: Skp2; carotid ligation; proliferation; ubiquitin-specific peptidase 10 (USP10); vascular smooth muscle cell (VSMC).

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Cell Line
Cell Movement
Cell Proliferation
Humans
Muscle, Smooth, Vascular / metabolism*
Myocytes, Smooth Muscle / metabolism*
Neointima / genetics
Neointima / metabolism*
Protein Stability
S-Phase Kinase-Associated Proteins / genetics
S-Phase Kinase-Associated Proteins / metabolism*
Ubiquitin Thiolesterase / genetics
Ubiquitin Thiolesterase / metabolism*

Substances

S-Phase Kinase-Associated Proteins
SKP2 protein, human
USP10 protein, human
Ubiquitin Thiolesterase