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Ubiquitin-Specific Protease 14 (USP14) Aggravates Inflammatory Response and Apoptosis of Lung Epithelial Cells in Pneumonia by Modulating Poly (ADP-Ribose) Polymerase-1 (PARP-1)

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Abstract

Pneumonia is one of the common respiratory diseases in pediatrics. Ubiquitin-specific protease 14 (USP14) contributes the progress of inflammation-associated diseases. Poly (ADP-ribose) polymerase-1 (PARP-1) involves in the signal transduction of inflammatory pulmonary disease. This study aims to identify the precise function and elaborate the regulatory mechanism of USP14/PARP-1 in the injury of lung epithelial cells. Human lung epithelial BEAS-2B cells received lipopolysaccharide (LPS) (0, 1, 5, and 10 mg/L) treatment for 16 h, establishing in vitro pneumonia model. USP14 protein and mRNA levels in LPS-injured lung epithelial cells were separately assessed using western blot and RT-qPCR analysis. Lung epithelial cells were transfected with siRNA-USP14 or OV-USP14 to perform gain- or loss-of-function experiments. CCK-8 assay was applied to assess cell viability. TUNEL staining and western blot analysis were adopted to determine cell apoptosis. In addition, release of inflammatory cytokines and nitric oxide (NO) was detected using the commercial kits. Meanwhile, PARP-1 protein levels in LPS-injured lung epithelial cells were detected by performing western blot assay. Moreover, Co-IP assay was utilized for detection of the interaction between USP14 and PARP-1. The regulatory effects of PARP-1 on USP14 function in LPS-injured lung epithelial cells were also investigated. LPS dose-dependently reduced viability of lung epithelial cells and elevated USP14 protein. USP14 combined with PARP-1 and increased PARP-1 expression. USP14 elevation exacerbated inflammatory injury and boosted the apoptosis of LPS-injured lung epithelial cells, which was reversed upon downregulation of PARP-1. To sum up, USP14 promotion exacerbated inflammatory injury and boosted the apoptosis of LPS-injured lung epithelial cells by upregulating PARP-1 expression. These findings may represent a therapeutic target for clinical intervention in pneumonia.

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Data availability

The analyzed data sets generated during the present study are available from the corresponding author on reasonable request.

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Funding

Wuhu Science and Technology Plan Project:2020ms3-2

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Author notes

  1. Chengcheng Huang and Hui Cao contributed equally to this work.

Authors and Affiliations

  1. Department of Pediatrics, Yijishan Hospital, Wannan Medical College, No. 2, West Road of Zheshan, Jinghu District, Anhui, 241001, Wuhu, China

    Chengcheng Huang, Fang Hu, Yong Gu, Changsheng Dou & Shifa Zhang

  2. Department of Obstetrics and Gynecology, Yijishan Hospital, Wannan Medical College, Wuhu, 241001, Anhui, China

    Hui Cao

  3. Department of Pediatrics, Yancheng No.1 Peoples’ Hospital, Yancheng, Jiangsu, China

    Jie Qin

  4. Department of Pediatrics, Suzhou Municipal Hospital, Suzhou, Jiangsu, China

    Lei Xu

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  1. Chengcheng Huang
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Contributions

Chengcheng Huang, Hui Cao, Jie Qin, Shifa Zhang, and Changsheng Dou designed the study. All the authors performed the experiments, analyzed the data, and wrote the manuscript. Chengcheng Huang, Hui Cao, Jie Qin, Shifa Zhang, and Changsheng Dou revised the manuscript.

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Correspondence to Changsheng Dou or Shifa Zhang.

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Huang, C., Cao, H., Qin, J. et al. Ubiquitin-Specific Protease 14 (USP14) Aggravates Inflammatory Response and Apoptosis of Lung Epithelial Cells in Pneumonia by Modulating Poly (ADP-Ribose) Polymerase-1 (PARP-1). Inflammation 44, 2054–2064 (2021). https://doi.org/10.1007/s10753-021-01482-3

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