Dexamethasone Upregulates the Expression of Aquaporin4 by Increasing SUMOylation in A549 Cells
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ORIGINAL ARTICLE
Dexamethasone Upregulates the Expression of Aquaporin4 by Increasing SUMOylation in A549 Cells Xiaoling Zhang,1,2 Xiaofang Ma,3,4 Yanxia Li,3,4 Weiheng Yan,2 Quan Zheng,3,4 Lili Li,4 Yulan Yan,5 Xiaozhi Liu,3,4,6 and Jun Zheng2,6
Abstract— Dexamethasone can alleviate the severity of bronchial and alveolar ede-
ma 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. KEY WORDS: dexamethasone; small ubiquitin-like modifiers (SUMOs); SUMOylation; A549; AQPs.
circulation. Pulmonary edema is a pathological condition in which excessive extravascular lung water accumulates in the alveoli [1]. Pulmonary edema presents in acute lung injury, and severe cases may develop into acute respiratory
INTRODUCTION Normally, there is a balance between the net fluid filtered and the fluid absorbed in the pulmonary Xiaozhi Liu and Jun Zheng contributed equally to this study, as cocorresponding authors. 1
Neonatal Intensive Care Unit, Guangzhou Women and Children Medical Center, Guangzhou, 510623, China 2 Department of Neonatology, Tianjin Central Hospital of Gynecology and Obstetrics, Tianjin, 300052, China 3 Central Laboratory, The Fifth Central Hospital of Tianjin, Tianjin, 300450, China
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Tianjin Key Laboratory of Epigenetics for Organ Development in Preterm Infants, The Fifth Central Hospital of Tianjin, Tianjin, 300450, China 5 Department of Hematology Oncology, The Fifth Central Hospital of Tianjin, Tianjin, 300450, China 6 To whom correspondence should be addressed to Xiaozhi Liu at Central Laboratory, The Fifth Central Hospital of Tianjin, Tianjin, 300450, China. E-mail: [email protected]; and ; [email protected]
0360-3997/20/0000-0001/0 # 2020 Springer Science+Business Media, LLC, part of Springer Nature
Zhang, Ma, Li, Yan, Zheng, Li, Yan, Liu, and Zheng distress syndrome [2]. Therefore, it is beneficial to inhibit pulmonary edema and alleviate lung injury in the early stages. Dexamethasone, a glucocorticoid hormone, has
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