{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T00:00:49Z","timestamp":1791158449788,"version":"4.1.0"},"reference-count":60,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2015,3,24]],"date-time":"2015-03-24T00:00:00Z","timestamp":1427155200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100011773","name":"Regional Council of Burgundy","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100011773","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2015,6]]},"abstract":"<jats:sec><jats:title>Background and Purpose<\/jats:title><jats:p>Leptin, an adipokine synthesized by the placenta during pregnancy, has been proposed for the management of preterm labour (<jats:styled-content style=\"fixed-case\">PTL<\/jats:styled-content>), as it is able to prevent <jats:italic>in vitro<\/jats:italic> uterine contractility and remodelling associated with labour onset. Another common feature of labour onset is the phenotypic switch of myometrial smooth muscle cells from a proliferative to a hypertrophic state. As proliferative effects have been demonstrated for leptin in other tissues, we aimed to investigate its ability to induce myometrial proliferation and thus to maintain uterine quiescence.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Approach<\/jats:title><jats:p>We stimulated human primary myometrial smooth muscle cells with leptin in the presence or absence of receptor antagonists or signalling pathway inhibitors.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>Leptin induced myometrial cell proliferation in a biphasic manner. At 6.25\u2009ng\u00b7mL<jats:sup>\u22121<\/jats:sup>, leptin\u2010induced proliferation was mediated by the leptin receptor and required the early activation of <jats:styled-content style=\"fixed-case\">ERK<\/jats:styled-content>1\/2. At a concentration above 25\u2009ng\u00b7mL<jats:sup>\u22121<\/jats:sup>, leptin induced direct non\u2010specific stimulation of the <jats:styled-content style=\"fixed-case\">IL\u20106<\/jats:styled-content> receptor, leading to <jats:styled-content style=\"fixed-case\">NF\u2010\u03baB<\/jats:styled-content> activation, and exerted anti\u2010proliferative effects. However, at 50\u2009ng\u00b7mL<jats:sup>\u22121<\/jats:sup>, leptin re\u2010induces proliferation via <jats:styled-content style=\"fixed-case\">IL\u20106<\/jats:styled-content> receptor stimulation that requires <jats:styled-content style=\"fixed-case\">STAT<\/jats:styled-content>3 and delayed <jats:styled-content style=\"fixed-case\">ERK<\/jats:styled-content>1\/2 activation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions and Implications<\/jats:title><jats:p>These data bring new insights into leptin signalling\u2010induced myometrial proliferation and its interrelationship with the <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u20106\/<jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u20106 receptor axis. In the light of our previous work, the present study emphasizes the potential value of leptin in the pharmacological management of <jats:styled-content style=\"fixed-case\">PTL<\/jats:styled-content> and it also strengthens the hypothesis that leptin might be a contributory factor in the parturition\u2010related disorders observed in obese women.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.13100","type":"journal-article","created":{"date-parts":[[2015,2,5]],"date-time":"2015-02-05T07:08:06Z","timestamp":1423120086000},"page":"2974-2990","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["EXPRESSION OF CONCERN: Dose\u2010dependent biphasic leptin\u2010induced proliferation is caused by non\u2010specific <scp>IL<\/scp>\u20106\/<scp>NF\u2010\u03baB<\/scp> pathway activation in human myometrial cells"],"prefix":"10.1111","volume":"172","author":[{"given":"Marina","family":"Barrichon","sequence":"first","affiliation":[{"name":"INSERM, U866, Equipe labellis\u00e9e ligue contre le Cancer and Association pour la Recherche contre le Cancer, and Laboratoire d'Excellence LipSTIC  Dijon France"},{"name":"Universit\u00e9 de Bourgogne  Dijon France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tarik","family":"Hadi","sequence":"additional","affiliation":[{"name":"INSERM, U866, Equipe labellis\u00e9e ligue contre le Cancer and Association pour la Recherche contre le Cancer, and Laboratoire d'Excellence LipSTIC  Dijon France"},{"name":"Universit\u00e9 de Bourgogne  Dijon France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maeva","family":"Wendremaire","sequence":"additional","affiliation":[{"name":"INSERM, U866, Equipe labellis\u00e9e ligue contre le Cancer and Association pour la Recherche contre le Cancer, and Laboratoire d'Excellence LipSTIC  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