USP7 is associated with greater disease activity in systemic lupus erythematosus via stabilization of the IFNα receptor

Yu,Ying; Su,Zhaoliang; Wang,Zhejiong; Xu,Huaxi

doi:10.3892/mmr.2017.6819

USP7 is associated with greater disease activity in systemic lupus erythematosus via stabilization of the IFNα receptor

Authors:
- Ying Yu
- Zhaoliang Su
- Zhejiong Wang
- Huaxi Xu
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Affiliations: Institute of Laboratory Medicine, Jiangsu Key Laboratory of Laboratory Medicine, Jiangsu University, Zhenjiang, Jiangsu 210013, P.R. China, Department of Laboratory Medicine, Chinese Medicine Hospital of Zhejiang, Hangzhou, Zhejiang 310006, P.R. China
Published online on: June 20, 2017 https://doi.org/10.3892/mmr.2017.6819
Pages: 2274-2280

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Abstract

An improved understanding of the mechanism of interferon (IFN)α activation in systemic lupus erythematosus (SLE) is likely to aid the identification of effective therapeutic targets. Increasing evidence has indicated that the activity of IFNα is mediated by the interplay of ubiquitylation/deubiquitylation enzyme regulators. The present study identified the deubiquitylation enzyme ubiquitin‑specific‑processing protease 7 (USP7) as a critical regulator of the human IFNα‑2 receptor (IFNAR1) protein levels. A co‑immunoprecipitation assay was used to demonstrate that USP7 was physically associated with IFNAR1 in vivo. A glutathione S‑transferase pull down assay revealed that USP7 interacted with IFNAR1 directly in vitro. Furthermore, USP7 may disassemble IFNAR1 dependent poly‑ubiquitin chains and stabilize IFNAR1 in vivo. The activation effects of USP7 on the IFNα pathway were confirmed by reverse transcription‑quantitative polymerase chain reaction and western blot analysis. Knockdown of USP7 expression consistently reduced the expression levels of signal transducer and activator of transcription (STAT)‑1, STAT‑2 and selected IFN‑inducible genes, including IFN‑induced protein with tetratricopeptide repeats 3, MX dynamin like GTPase 1 and 2'‑5'‑oligoadenylate synthetase 1. The present study demonstrated that USP7 was significantly overexpressed in 210 SLE patients compared with healthy controls. Furthermore, the association between USP7 levels, IFN scores, SLE disease activity index scores and anti‑double stranded DNA were analyzed and, as expected, positive correlations were demonstrated, indicating that USP7 may be associated with SLE disease activity through the stabilization of IFNAR1.

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