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The Interaction of OTUB1 and TRAF3 Mediates NLRP3 Inflammasome Activity to Regulate TGF-β1-induced BEAS-2B Cell Injury

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Abstract

Asthma is a frequently chronic respiratory disease with inflammation and remodeling in the airway. OTUB1 has been reported to be associated with pulmonary diseases. However, the role and potential mechanism of OTUB1 in asthma remain unclear. The expressions of OTUB1 in the bronchial mucosal tissues of asthmatic children and TGF-β1-induced BEAS-2B cells were determined. The biological behaviors were assessed in an asthma in vitro model using a loss-function approach. The contents of inflammatory cytokines were detected by ELISA kits. The related protein expressions were performed using western blot assay. Besides, the interaction between OTUB1 and TRAF3 was detected by Co-IP and ubiquitination assays. Our results showed that OTUB1 level was increased in asthmatic bronchial mucosal tissues and TGF-β1-induced BEAS-2B cells. OTUB1 knockdown promoted proliferation, inhibited apoptosis and EMT of TGF-β1-treated cells. The inhibition of OTUB1 attenuated the TGF-β1-induced inflammation and remodeling. Furthermore, OTUB1 knockdown inhibited the deubiquitination of TRAF3 and further suppressed the activation of NLRP3 inflammasome. The overexpression of TRAF3 or NLRP3 reversed the positive role of OTUB1 knockdown in TGF-β1-induced cells injury. Collectively, OTUB1 deubiquitinates TRAF3 to activate NLRP3 inflammasome, thereby leading to inflammation and remodeling of TGF-β1-induced cells, and further promoting the pathogenesis of asthma.

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Data Availability

The data and materials used to support the findings of this study are available from the corresponding author on reasonable request.

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Funding

This study was supported by Scientific Research Support Project of Xi’an Children’s Hospital (NO. 2020C10).

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Authors and Affiliations

  1. Department of Respiratory and Critical Care Medicine, Shaanxi Provincial People’s Hospital, Xi’an, 710068, Shaanxi, China

    Liqun Shang, Yujie Du, Yali Zhao & Yongqing Zhang

  2. Department of Respiratory and Asthma, Xi’an Children’s Hospital, Xi’an, 710003, Shaanxi, China

    Cuicui Liu

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All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by Liqun Shang, Yujie Du, Yali Zhao, Yongqing Zhang, Cuicui Liu. The first draft of the manuscript was written by Liqun Shang and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

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Correspondence to Cuicui Liu.

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Shang, L., Du, Y., Zhao, Y. et al. The Interaction of OTUB1 and TRAF3 Mediates NLRP3 Inflammasome Activity to Regulate TGF-β1-induced BEAS-2B Cell Injury. Appl Biochem Biotechnol 195, 7060–7074 (2023). https://doi.org/10.1007/s12010-023-04434-9

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