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Aberrant intrauterine inflammation and infection are known to augment the synthesis of proinflammatory cytokines and induce uterine contractions, which can subsequently lead to preterm birth. The transforming growth factor-\n                    <jats:italic>\u03b2<\/jats:italic>\n                    (TGF-\n                    <jats:italic>\u03b2<\/jats:italic>\n                    ) superfamily members regulate numerous cellular processes through the activation of intracellular mediators known as mothers against decapentaplegic homolog (SMADs). Studies in nongestational tissues have shown that SMAD3 plays a role in immune regulation and inflammation; however, its role in human labour remains unknown. Thus, the present study aimed at (i) characterising the expression of SMAD3 in the human myometrium; (ii) determining the effect of bacterial and viral products and proinflammatory cytokines on SMAD3 transcriptional activity in primary human myometrial cells; and (iii) investigating the effect of SMAD3 siRNA knockdown on the production of prolabour mediators in primary human myometrial cells. Phosphorylated (i.e., active) SMAD3 protein expression was lower in the myometrium after spontaneous term labour compared to the myometrium from nonlabouring women. Using a luciferase assay, the proinflammatory cytokines IL-1\n                    <jats:italic>\u03b2<\/jats:italic>\n                    and TNF, and viral analogue polyinosinic\u2009:\u2009polycytidylic acid (poly(I\u2009:\u2009C)) significantly reduced SMAD3 transcriptional activity in human primary myometrial cells. Loss-of-function studies found that SMAD3 knockdown in myometrial cells significantly increased IL-1\n                    <jats:italic>\u03b2<\/jats:italic>\n                    - and poly(I\u2009:\u2009C)-induced proinflammatory cytokines (IL-1A, IL-6), chemokines (IL-8, MCP-1), the adhesion molecule ICAM-1, COX-2 mRNA expression, and subsequent PGF\n                    <jats:sub>\n                      2\n                      <jats:italic>\u03b1<\/jats:italic>\n                    <\/jats:sub>\n                    release. In conclusion, SMAD3 deficiency is associated with increased production of proinflammatory and prolabour mediators in the human myometrium.\n                  <\/jats:p>","DOI":"10.1155\/2018\/3140420","type":"journal-article","created":{"date-parts":[[2018,9,27]],"date-time":"2018-09-27T19:32:56Z","timestamp":1538076776000},"page":"1-11","source":"Crossref","is-referenced-by-count":6,"title":["Identification of SMAD3 as a Novel Mediator of Inflammation in Human Myometrium\n                    <i>In Vitro<\/i>"],"prefix":"10.1155","volume":"2018","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4744-6929","authenticated-orcid":true,"given":"Martha","family":"Lappas","sequence":"first","affiliation":[{"name":"Obstetrics, Nutrition, and Endocrinology Group, Department of Obstetrics and Gynaecology, University of Melbourne, Victoria, Australia"},{"name":"Mercy Perinatal Research Centre, Mercy Hospital for Women, Heidelberg, Victoria, 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