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RETRACTED ARTICLE: Stabilization of the histone acetyltransferase Tip60 by deubiquitinating enzyme USP7 stimulates the release of pro-inflammatory mediators in acute lung injury

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This article was retracted on 23 June 2022

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Abstract

Acute lung injury (ALI) is often associated with inflammation. Increasing evidence has identified the role for ubiquitin-specific protease 7 (USP7) in activating the expression of inflammatory factors in macrophages. The present study evaluated whether USP7 also mediates histone acetyltransferase Tat-interactive protein 60 (Tip60) in the development of ALI inflammation. An ALI mouse model was induced by intratracheal lipopolysaccharide (LPS) administration. Next, lung myeloperoxidase (MPO) activity and the ratio of dry weight/wet weight of lung were examined to evaluate tissue damage. In addition, RAW 264.7 cells were treated with LPS to induce an in vitro LPS-induced inflammatory cell model. ELISA was performed to measure expression of IL-1β, TNF-α, IL-6, and IL-8 in cells and tissues. TUNEL was used to detect LPS-induced cell apoptosis. Furthermore, the interaction between USP7 and Tip60 was identified by IP, Western blot analysis, and cycloheximide (CHX) treatment. The enrichment of Tip60 and H3K27ac in the promoter region of IL-6 and IL-8 was assessed by ChIP. USP7 was highly expressed in LPS-endotoxin-induced ALI mouse models and silencing of USP7 delayed the progression of ALI in mice. Silencing of USP7 protected RAW 264.7 cells against LPS-induced inflammation and apoptosis by downregulating IL-1β, TNF-α, IL-6, and IL-8. USP7 enhanced Tip60 protein stability, and Tip60 increased the enrichment of H3K27ac on IL-6 and IL-8 promoter region and activated NF-κB p65 to increase IL-6 and IL-8 expression. These findings reveal a new post-transcriptional role for USP7 in inflammation by stabilizing Tip60 and increasing the release of the pro-inflammatory cytokines, and implicate USP7 inhibitors as potential therapeutic agents for ALI.

Key messages

  • USP7 expresses highly in an acute lung injury (ALI) mouse models.

  • Silencing of USP7 inhibits inflammation and cell apoptosis in ALI mouse.

  • USP7 stabilizes Tip60 to boost the release of IL-6 and IL-8.

  • Tip60 increases IL-6 and IL-8 expression by acetylating NF-κB p65.

  • Silencing of USP7 alleviates ALI by repressing NF-κB p65 and Tip60.

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Acknowledgments

We give our sincere gratitude to the reviewers for their valuable suggestions.

Funding

This study was supported by the International Science and Technology Cooperation Project of Jilin Province (No. 20190701068GH).

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Authors and Affiliations

  1. Department of Respiratory Medicine, China-Japan Union Hospital of Jilin University, Changchun, 130033, People’s Republic of China

    Jing Wang

  2. Department of Infections, China-Japan Union Hospital of Jilin University, Changchun, 130033, People’s Republic of China

    Hong-Yan Li

  3. Department of Anesthesiology, China-Japan Union Hospital of Jilin University, No. 126, Xiantai Street, Changchun, 130033, Jilin Province, People’s Republic of China

    Zhen-Bo Su

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  1. Jing Wang
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Contributions

Jing Wang designed the study. Hong-Yan Li collated the data, carried out data analyses, and produced the initial draft of the manuscript. Zhen-Bo Su contributed to drafting the manuscript. All authors have read and approved the final submitted manuscript.

Corresponding author

Correspondence to Zhen-Bo Su.

Ethics declarations

The animal experiments were performed strictly in accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals from the National Institutes of Health. The protocol of animal experiments was approved by the Institutional Animal Care and Use Committee of China-Japan Union Hospital of Jilin University. The animal experiments were conducted with an aim to minimize the number and discomfort of experimental animals.

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This article has been retracted. Please see the retraction notice for more detail: https://doi.org/10.1007/s00109-022-02225-z

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Wang, J., Li, HY. & Su, ZB. RETRACTED ARTICLE: Stabilization of the histone acetyltransferase Tip60 by deubiquitinating enzyme USP7 stimulates the release of pro-inflammatory mediators in acute lung injury. J Mol Med 98, 907–921 (2020). https://doi.org/10.1007/s00109-020-01910-1

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  • DOI: https://doi.org/10.1007/s00109-020-01910-1

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