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Dexamethasone Upregulates the Expression of Aquaporin4 by Increasing SUMOylation in A549 Cells

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Abstract

Dexamethasone can alleviate the severity of bronchial and alveolar edema and therefore is widely applied in the treatment of various exudative diseases including pulmonary edema. However, the effectiveness of dexamethasone is still being questioned and its mechanism is not fully understood. Aquaporins (AQPs) are mainly responsible for the transmembrane transport of water, which is tightly associated with pulmonary edema. Small ubiquitin-like modifiers (SUMOs) are considered to play a protective role in some pathological conditions. In this study, we demonstrated that dexamethasone can upregulate the expression of AQPs in A549 cells by inducing SUMOylation. We found that a low dose of dexamethasone significantly upregulated the levels of SUMOylation and AQP expression in A549 cells, accompanied by a translocation of SUMOs from the cytoplasm to the nucleus. We also explored the possible relation between SUMOylation and AQPs. Knockdown of SUMO2/3 by RNA interference decreased the level of AQP4 in A549 cells after dexamethasone stimulation. Together, our findings demonstrated that AQP4 expression was upregulated in A549 cells exposed to dexamethasone, and SUMOylation may participate in the regulation of AQP4.

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Data Availability

The datasets used and analyzed are available from the corresponding author on reasonable request.

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Acknowledgments

The authors would like to thank Dr. Xiaozhi Liu and Xiaofang Ma (Central laboratory, Tianjin Fifth Central Hospital, Tianjin, China) for their help with experimental design. All authors read and approved the final manuscript. We thank Liwen Bianji, Edanz Group China (www.liwenbianji.cn/ac), for editing the English text of a draft of this manuscript.

Funding

This study was supported by the National Natural Science Foundation of China (grant no. 81872184), the Tianjin Natural Science Foundation (grant no. 18JCQNJC12800), and the Tianjin Binhai New Area Health and Family Planning Commission Science and Technology Projects (grant nos. 2015BWKY001 and 2016BWKY026).

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Author notes

  1. Xiaozhi Liu and Jun Zheng contributed equally to this study, as co-corresponding authors.

Authors and Affiliations

  1. Neonatal Intensive Care Unit, Guangzhou Women and Children Medical Center, Guangzhou, 510623, China

    Xiaoling Zhang

  2. Department of Neonatology, Tianjin Central Hospital of Gynecology and Obstetrics, Tianjin, 300052, China

    Xiaoling Zhang, Weiheng Yan & Jun Zheng

  3. Central Laboratory, The Fifth Central Hospital of Tianjin, Tianjin, 300450, China

    Xiaofang Ma, Yanxia Li, Quan Zheng & Xiaozhi Liu

  4. Tianjin Key Laboratory of Epigenetics for Organ Development in Preterm Infants, The Fifth Central Hospital of Tianjin, Tianjin, 300450, China

    Xiaofang Ma, Yanxia Li, Quan Zheng, Lili Li & Xiaozhi Liu

  5. Department of Hematology Oncology, The Fifth Central Hospital of Tianjin, Tianjin, 300450, China

    Yulan Yan

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  1. Xiaoling Zhang
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Correspondence to Xiaozhi Liu or Jun Zheng.

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Zhang, X., Ma, X., Li, Y. et al. Dexamethasone Upregulates the Expression of Aquaporin4 by Increasing SUMOylation in A549 Cells. Inflammation 43, 1925–1935 (2020). https://doi.org/10.1007/s10753-020-01267-0

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  • DOI: https://doi.org/10.1007/s10753-020-01267-0

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