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Title: Activation of the epithelial sodium channel (ENaC) leads to cytokine profile shift to pro-inflammatory in labor
Authors: Sun, X
Guo, JH 
Zhang, D
Chen, JJ 
Lin, WY
Huang, Y
Chen, H
Huang, WQ
Liu, YF
Tsang, LL
Yu, MK 
Chung, YW
Jiang, XH
Huang, HF
Chan, HC
Ruan, YC 
Keywords: ENaC
Preterm labor
Issue Date: 2018
Publisher: Wiley-Blackwell
Source: EMBO molecular medicine, Oct. 2018, v. 10, no. 10, e8868, p. 1-15 How to cite?
Journal: EMBO molecular medicine 
Abstract: The shift of cytokine profile from anti- to pro-inflammatory is the most recognizable sign of labor, although the underlying mechanism remains elusive. Here, we report that the epithelial sodium channel (ENaC) is upregulated and activated in the uterus at labor in mice. Mechanical activation of ENaC results in phosphorylation of CREB and upregulation of pro-inflammatory cytokines as well as COX-2/PGE(2) in uterine epithelial cells. ENaC expression is also upregulated in mice with RU486-induced preterm labor as well as in women with preterm labor. Interference with ENaC attenuates mechanically stimulated uterine contractions and significantly delays the RU486-induced preterm labor in mice. Analysis of a human transcriptome database for maternal-fetus tissue/blood collected at onset of human term and preterm births reveals significant and positive correlation of ENaC with labor-associated pro-inflammatory factors in labored birth groups (both term and preterm), but not in non-labored birth groups. Taken together, the present finding reveals a pro-inflammatory role of ENaC in labor at term and preterm, suggesting it as a potential target for the prevention and treatment of preterm labor.
ISSN: 1757-4676
EISSN: 1757-4684
DOI: 10.15252/emmm.201808868
Rights: © 2018 The Authors. Published under the terms of the CC BY 4.0 license
This is an open access article under the terms of the Creative Commons Attribution 4.0 License (, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
The following publication Sun, X., Guo, J.H., Zhang, D., Chen, J.J., Lin, W.Y., Huang, Y., ... & Ruan, Y.C. (2018). Activation of the epithelial sodium channel (ENaC) leads to cytokine profile shift to pro-inflammatory in labor. EMBO molecular medicine, 10 (10), e8868, p. 1-15 is available at
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