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However, the link between inflammation and the onset of labor remains incompletely understood. We identified the transient receptor potential vanilloid 4 (TRPV4) channel as a critical regulator of myometrial calcium (Ca\n                    <jats:sup>2+<\/jats:sup>\n                    ) entry and contractility. In this study, we aimed to determine if the TRPV4 channel regulates uterine inflammation and its subsequent effects on myometrial contractility in experimental preterm labor. We demonstrated that global loss of TRPV4 protected mice against inflammation\u2010induced preterm labor, decreased baseline myometrial contractility, and diminished lipopolysaccharide\u2010stimulated increases in oxytocin\u2010mediated contraction. Pharmacological inhibition of TRPV4 in human myometrial smooth muscle cells (SMC) blunted lipopolysaccharide (LPS)\u2010induced activation of nuclear factor kappa\u2010B (NF\u03baB) and pro\u2010inflammatory cytokine expression. In contrast, pharmacologic activation of TRPV4 augmented LPS\u2010induced NF\u03baB activation. Further, TRPV4\u2010mediated NF\u03baB activation was dependent on extracellular Ca\n                    <jats:sup>2+<\/jats:sup>\n                    entry in myometrial SMC. Together, these data show that extracellular Ca\n                    <jats:sup>2+<\/jats:sup>\n                    entry via TRPV4 potentiates NF\u03baB\u2010mediated inflammation and increases susceptibility to preterm labor. The ability of TRPV4 to modulate both myometrial inflammation and contractility, processes central to the onset of preterm and term labor, suggests that the TRPV4 channel may represent a novel therapeutic target for the treatment of premature birth.\n                  <\/jats:p>","DOI":"10.1096\/fj.202402949r","type":"journal-article","created":{"date-parts":[[2025,3,10]],"date-time":"2025-03-10T01:18:13Z","timestamp":1741569493000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Loss of\n                    <scp>TRPV4<\/scp>\n                    decreases\n                    <scp>NF\u03baB<\/scp>\n                    \u2010mediated myometrial inflammation and prevents preterm labor"],"prefix":"10.1096","volume":"39","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9916-8740","authenticated-orcid":false,"given":"Judith A.","family":"Ingles","sequence":"first","affiliation":[{"name":"Center for Excellence in 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