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/PGE₂ 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.

细胞因子谱从抗炎到促炎的转变是最可识别的分娩迹象，尽管其潜在机制仍然难以捉摸。在这里，我们报道小鼠上班时子宫中的上皮钠通道（EN aC）被上调和激活。EN aC的机械激活导致子宫上皮细胞中CREB的磷酸化和促炎性细胞因子以及COX -2- PGE _2的上调。在患有RU 486引起的早产的小鼠以及有早产的妇女中，EN aC表达也被上调。干扰ENaC减弱了机械刺激的子宫收缩，并显着延迟了RU 486诱导的小鼠早产。对人类足月和早产开始时收集的母胎组织/血液的人类转录组数据库的分析显示，EN aC与分娩早产组（足月和早产）中与劳动相关的促炎因子显着正相关，但是不在未分娩的出生人群中。综上所述，本发现揭示了EN aC在足月和早产中的促炎作用，表明它是预防和治疗早产的潜在目标。