Liong Stella, Barker Gillian, Lappas Martha
Obstetrics, Nutrition and Endocrinology Group, Department of Obstetrics and Gynaecology, University of Melbourne, Victoria, Australia; Mercy Perinatal Research Centre, Mercy Hospital for Women, Victoria, Australia.
Obstetrics, Nutrition and Endocrinology Group, Department of Obstetrics and Gynaecology, University of Melbourne, Victoria, Australia; Mercy Perinatal Research Centre, Mercy Hospital for Women, Victoria, Australia.
Placenta. 2017 May;53:101-112. doi: 10.1016/j.placenta.2017.04.010. Epub 2017 Apr 13.
Obesity is a growing epidemic, and as a consequence the number of obese pregnancies has also increased. Pregnancy is characterised by maternal and placental inflammation which is intensified with maternal obesity. The proviral integration site for Moloney murine leukemic virus (Pim)-1 protein is a serine/threonine kinase involved in a wide range of inflammatory diseases. In relation to obesity, however, its role has not been elucidated in human placenta. The aims were to determine the placental expression of Pim-1 with pre-existing maternal obesity and its role in regulating placental inflammation associated with obesity.
Human placenta was obtained at the time of term Caesarean section from lean and pre-existing obese pregnant women to determine the effect of maternal obesity on Pim-1 expression. To determine the effect of Pim-1 on the inflammatory response induced by bacterial endotoxin LPS and pro-inflammatory cytokines TNF-α or IL-1β, the chemical inhibitor SMI-4a and siRNA were used.
Pim-1 protein and mRNA expression was significantly increased in placenta of obese women. SMI-4a significantly suppressed the expression and release of pro-inflammatory cytokine IL-6 and chemokines GRO-α and MCP-1 when stimulated with LPS or TNF-α in placenta. Primary trophoblast cells transfected with Pim-1 siRNA had decreased expression and release of pro-inflammatory cytokines IL-1β, IL-6, chemokines GRO-α and MCP-1, when stimulated with LPS, TNF-α or IL-1β.
The findings from this study implicate Pim-1 may contribute to placental inflammation in pregnancies complicated by maternal obesity. Thus, therapeutic targets for Pim-1 may improve fetal outcomes complicated by obese pregnancies.
肥胖症正日益流行，因此肥胖孕妇的数量也有所增加。妊娠的特点是母体和胎盘炎症，而母体肥胖会加剧这种炎症。莫洛尼氏鼠白血病病毒（Pim）-1蛋白的前病毒整合位点是一种丝氨酸/苏氨酸激酶，参与多种炎症性疾病。然而，关于肥胖症，其在人胎盘中的作用尚未阐明。本研究的目的是确定孕前肥胖孕妇胎盘中Pim-1的表达及其在调节与肥胖相关的胎盘炎症中的作用。
在足月剖宫产时从体型正常和孕前肥胖的孕妇获取人胎盘，以确定母体肥胖对Pim-1表达的影响。为了确定Pim-1对细菌内毒素LPS和促炎细胞因子TNF-α或IL-1β诱导的炎症反应的影响，使用了化学抑制剂SMI-4a和小干扰RNA（siRNA）。
肥胖女性胎盘中Pim-1蛋白和mRNA表达显著增加。在胎盘受到LPS或TNF-α刺激时，SMI-4a显著抑制促炎细胞因子IL-6以及趋化因子GRO-α和MCP-1的表达和释放。用Pim-1 siRNA转染的原代滋养层细胞在受到LPS、TNF-α或IL-1β刺激时，促炎细胞因子IL-1β、IL-6、趋化因子GRO-α和MCP-1的表达和释放减少。
本研究结果表明，Pim-1可能在合并母体肥胖的妊娠中导致胎盘炎症。因此，针对Pim-1的治疗靶点可能改善肥胖妊娠相关的胎儿结局。
