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Wip1 Aggravates the Cerulein-Induced Cell Autophagy and Inflammatory Injury by Targeting STING/TBK1/IRF3 in Acute Pancreatitis

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Abstract

Acute pancreatitis (AP) is an inflammatory reaction of pancreatic tissue self-digestion, edema, hemorrhage, and even necrosis after the activation of pancreatic enzymes in the pancreas caused by a variety of etiologies. This study was aimed to explore the functions and mechanism of Wip1 in AP. Twenty male SD rats were randomly assigned into 2 groups (control group: saline treatment; AP group: cerulein treatment). And cerulein-treated AR42J cells were conducted as AP model in vitro. The levels of amylase were detected by using the Beckman biochemical analyzer. The levels of IFNβ and TNFα were analyzed by ELISA. The autophagosomes were observed by transmission electron microscopy. The Wip1-specific shRNAs were transfected to AR42J cells to silence the expression of Wip1. The levels of Wip1 were measured by qRT-PCR and Western blot. The levels of STING/TBK1/IRF3 and LC3 were measured by Western blot. The AP model was successfully constructed by cerulein administration. Wip1 was notably upregulated in AP models. Autophagy and STING pathway activation were involved in the development of AP. Wip1 inhibition counteracts the promotion effect on inflammatory response induced by cerulein in AR42J Cells. Wip1 inhibition inhibited the activity of the STING/TBK1/IRF3 and reduced LC3 levels in AP. This study preliminarily explored that Wip1 could regulate autophagy and participate in the development of AP through the STING/TBK1/IRF3 signaling pathway.

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Funding

This work was financially supported by following funds: the National Natural Science Foundation of China (No.81902017) and the Project of Improving the Diagnosis and Treatment Capacity of Hepatobiliary, Pancreas and Intestine in Hunan Province (Xiangwei [2019] No. 118).

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Data and materials are included in the manuscript.

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Authors and Affiliations

  1. Department of Hepatobiliary Surgery, Hunan Research Center of Biliary Disease, Hunan Provincial People’s Hospital, The First Affiliated Hospital of Hunan Normal University, Changsha, Hunan Province, China

    Yinghui Song, Zhihua Zhang, Zhangtao Yu, Guoyi Xia, Yizhi Wang, Le Wang, Chuang Peng, Bo Jiang & Sulai Liu

  2. Biliary Disease Research Laboratory of Hunan Provincial People’s Hospital, Key Laboratory of Hunan Normal University, Changsha, Hunan Province, China

    Yinghui Song, Zhihua Zhang, Zhangtao Yu, Guoyi Xia, Yizhi Wang, Le Wang, Chuang Peng, Bo Jiang & Sulai Liu

  3. Clinical Medical Technology Research Center of Hunan Provincial for Biliary Disease Prevention and Treatment, Changsha, Hunan Province, China

    Yinghui Song, Zhihua Zhang, Zhangtao Yu, Guoyi Xia, Yizhi Wang, Le Wang, Chuang Peng, Bo Jiang & Sulai Liu

Authors
  1. Yinghui Song
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  2. Zhihua Zhang
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  3. Zhangtao Yu
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  6. Le Wang
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  7. Chuang Peng
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  8. Bo Jiang
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  9. Sulai Liu
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Contributions

Yinghui Song, Zhihua Zhang, Zhangtao Yu, and Yizhi Wang performed the experiment; Yinghui Song, Guoyi Xia, and Le Wang contributed significantly to analysis and manuscript preparation; Chuang Peng performed the data analyses and wrote the manuscript; Bo Jiang and Sulai Liu contributed to the conception of the study; and Yinghui Song helped perform the analysis with constructive discussions.

Corresponding author

Correspondence to Sulai Liu.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. This study was approved by the ethical committee of Hunan Normal University. Informed consent was obtained from all individual participants included in the study.

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Song, Y., Zhang, Z., Yu, Z. et al. Wip1 Aggravates the Cerulein-Induced Cell Autophagy and Inflammatory Injury by Targeting STING/TBK1/IRF3 in Acute Pancreatitis. Inflammation 44, 1175–1183 (2021). https://doi.org/10.1007/s10753-021-01412-3

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  • DOI: https://doi.org/10.1007/s10753-021-01412-3

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