PIEZO channels link mechanical forces to uterine contractions in parturition

• 成果类型: Article
• 署名作者: Zhang, Yunxiao; Kini, Sejal A.; Mishkanian, Sassan A.; Yarishkin, Oleg; Luo, Renhao; Seradj, Saba Heydari; Leung, Verina H.; Wang, Yu; Servin-Vences, M. Rocio; Keenan, William T.; Sonmez, Utku; Sanchez-Alavez, Manuel; Liu, Yuejia; Jin, Xin; Lipomi, Darren J.; Ye, Li; Petrascheck, Michael; Frolova, Antonina I.; England, Sarah K.; Patapoutian, Ardem
• 署名单位: Scripps Research Institute; Howard Hughes Medical Institute; University of California System; University of California San Diego; Scripps Research Institute; Universidad Autonoma de Baja California
• 刊物名称: SCIENCE
• ISSN/ISSBN: 0036-8075; 1095-9203
• DOI: 10.1126/science.ady3045
• 发表日期: 2025-11-13
• 页码: eady3045
• 关键词: smooth-muscle-cells; expression; CONNEXIN-43; pregnancy; stretch; reflex; myometrium; neurons; LABOR

摘要

Mechanical forces are extensively involved in pregnancy and parturition, but their precise roles and mechanisms remain poorly understood. We identified mechanically activated ion channels PIEZO1 and PIEZO2 as key mechanotransducers required for labor progression. Genetic deletion of Piezo1 and Piezo2 in mice resulted in weakened uterine contractions and severe parturition defects. Tissue-specific knockouts revealed that deletion in either uterus or sensory neurons alone caused modest defects whereas combined loss markedly impaired labor, demonstrating additive effects. Single-nuclei sequencing indicated that loss of PIEZO function reduced expression of connexin43 (Gja1), a gap junction protein in uterine smooth muscle cells, suggesting a mechanistic link to impaired contraction. These findings highlight the critical role of PIEZO channels in mechanotransduction during parturition and suggest therapeutic targets for labor dysfunction.