Research Paper Advance Articles
USP10 deletion inhibits macrophage-derived foam cell formation and cellular-oxidized low density lipoprotein uptake by promoting the degradation of CD36
- 1 Guangzhou Institute of Cardiovascular Disease, Guangdong Key Laboratory of Vascular Diseases, State Key Laboratory of Respiratory Disease, The Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong, China
- 2 Guangzhou Municipal and Guangdong Provincial Key Laboratory of Protein Modification and Degradation, School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou, China
Received: March 28, 2020 Accepted: August 14, 2020 Published: November 10, 2020https://doi.org/10.18632/aging.104003
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Copyright: © 2020 Xia et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Foam cell formation process is involved in the pathogenesis of atherosclerosis (AS). Activation of this biological process depends on lipid uptake by scavenger receptors, such as CD36, SR-A and SR-B1. Among these receptors, CD36 is the principal one because it dominates roughly 50% lipid uptake in monocytes. In this study, our western blotting and RT-qPCR assays revealed that USP10 inhibition promotes the degradation of CD36 protein but does not change its mRNA level. In addition, Co-IP results showed that USP10 interacts with CD36 and stabilizes CD36 protein by cleaving poly-ubiquitin on CD36. Significantly, USP10 promotes foam cell formation. Immunofluorescence and Oil red O staining assays show that inhibition or knockdown of USP10 suppresses lipid uptake and foam cell formation by macrophages. In conclusion, USP10 promotes the development and progression of atherosclerosis through stabilizing CD36 protein expression. The regulation of USP10-CD36 may provide a significant therapeutic scheme in atherosclerosis.
AS: atherosclerosis; UPS: ubiquitin proteasome system; oxLDL: oxidized low-density lipoprotein; SR-A: scavenger receptor-A; Lox-1: lectin-like oxLDL receptor 1; ABCA1: ATP-binding cassette transporters A1; ABCG1: ATP-binding cassette transporters G1; SR-B1: scavenger receptor class B type 1; DUBs: deubiquitinases; USP10: Ubiquitin-specificpeptidase 10; CHX: cycloheximide; Co-IP: co-immunoprecipitation; IB: immunoblot.