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Recent work has identified the transient receptor potential vanilloid 4 (TRPV4) channel, a membrane calcium channel upregulated in uterine smooth muscle through gestation, as integral in the transition from quiescence to contraction in the gravid uterus. The present study builds upon these findings and investigates regulation of the TRPV4 channel during pregnancy in the murine and human uterus by micro\u2010RNA 203 (miR\u2010203). We find a progressive decrease in miR\u2010203 expression during gestation, accompanied by a reciprocal increase in TRPV4 mRNA and protein expression. In human uterine smooth muscle cells (UtSMC), miR\u2010203 overexpression reduces, and si\u2010RNA\u2010mediated silencing increases, TRPV4 expression. Studies using murine UtSMC demonstrate that miR\u2010203 expression modulates TRPV4\u2010mediated cytosolic calcium entry and contractility. Consistent with these findings, the response to pharmacologic TRVP4 agonists is increased in myometrial tissue from miRNA203\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice compared to control mice. Moreover, we demonstrate that miR\u2010203 binds specifically on the promoter region of TRPV4 to decrease expression. In murine inflammatory models of preterm labor, miR\u2010203 overexpression prolongs pregnancy. Estradiol (E2) decreases miR\u2010203 and increases TRPV4 expression, providing a potential physiologic link for the unique reciprocal relationship in UtSMC. Taken together, these findings provide evidence that miR\u2010203 modulates uterine contractility during pregnancy via negative regulation of TRPV4. These findings support the hypothesis that targeting miR\u2010203 holds the promise of an entirely novel approach to prevent prematurity and treat preterm labor.\n                  <\/jats:p>","DOI":"10.1096\/fj.202401783rr","type":"journal-article","created":{"date-parts":[[2024,11,15]],"date-time":"2024-11-15T08:39:08Z","timestamp":1731659948000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["<scp>miR<\/scp>\n                    \u2010203 modulates pregnant myometrium contractility via transient receptor potential vanilloid 4 channel expression"],"prefix":"10.1096","volume":"38","author":[{"given":"Lihua","family":"Ying","sequence":"first","affiliation":[{"name":"Division of Pulmonary, Asthma, and Sleep Medicine Stanford University School of Medicine  Stanford California 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