Cannabidiol modulates PIEZO1 activity to regulate uterine contractility and pregnancy outcome
摘要
Preterm birth is the leading cause of mortality in children under five worldwide. Aberrant uterine contractions, driven by calcium-dependent excitability of myometrial smooth muscle cells, are central to preterm labor. Current tocolytic agents target calcium signaling but pose cardiovascular risks to both mother and fetus. Here, we identify the mechanosensitive cation channel PIEZO1 as a key regulator of myometrial contractility. Activation of PIEZO1 elevates intracellular Ca2+ and triggers contraction in primary human myometrial smooth muscle cells and mouse uterine tissue. We further show that cannabidiol (CBD) acts as a potent PIEZO1 inhibitor, blocking Ca2+ influx and suppressing uterine contractions. In two mouse models of preterm birth, CBD markedly reduced myometrial contractility, delayed delivery, and improved fetal outcomes. These findings reveal an essential role for PIEZO1 in uterine contractility and highlight CBD-mediated PIEZO1 inhibition as a potential therapeutic strategy for preventing preterm labor.
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