Berry Elicia B E, Eykholt Roberta, Helliwell Rachel J A, Gilmour R Stewart, Mitchell Murray D, Marvin Keith W
The Liggins Institute, University of Auckland, Private Bag 92019, Auckland, New Zealand.
Mol Pharmacol. 2003 Dec;64(6):1586-90. doi: 10.1124/mol.64.6.1586.
Peroxisome proliferator-activated receptors (PPARs) are a family of nuclear receptors that are involved in lipid metabolism, differentiation, proliferation, cell death, and inflammation. Three subtypes have been identified: PPAR-alpha, -delta, and -gamma. We have previously shown presence of PPAR-gamma mRNA in the amnion, choriodecidua, and placenta, and its level of expression was unchanged with labor. To evaluate whether PPAR-alpha and -delta subtypes are present in intrauterine tissues, placentae were obtained from women at term after spontaneous vaginal delivery (TSL; n = 15) and elective caesarean section before labor (TNL; n = 15). Northern blot analyses were used to evaluate the mRNA for PPARs. Activities of PPARs were assessed using JEG3 choriocarcinoma cells transfected with a PPAR-response element reporter construct (pTK-PPREx3-luc) and treated with PPAR ligands. The PPAR-gamma-specific ligand rosiglitazone induced PPAR response element (PPRE)-mediated activity in a concentration-dependent manner, whereas the PPAR-gamma-specific irreversible inhibitor GW9662 fully inhibited this induction. However, GW9662 only partially inhibited 15-deoxy-Delta12,14-prostaglandin J2 (15d-PGJ2)-induced luciferase activity, suggesting that 15d-PGJ2 may also activate either of the other isoforms. PPAR-alpha and -delta are expressed in the amnion, choriodecidua, and placental villous tissues. In the amnion, although for PPAR-alpha no significant difference in expression was observed with labor, PPAR-delta expression increased significantly (p < 0.001). In the choriodecidua, expression of PPAR-alpha declined with labor (p < 0.01), whereas, as in the amnion, PPAR-delta expression increased (p < 0.05). In the placenta, both PPAR-alpha and -delta expression increased with labor (p < 0.005). The changes observed with labor suggest that regulation of PPAR expression and function may have roles to the mechanisms that maintain pregnancy or initiate labor.
过氧化物酶体增殖物激活受体（PPARs）是一类核受体，参与脂质代谢、分化、增殖、细胞死亡和炎症反应。已鉴定出三种亚型：PPAR-α、-δ和-γ。我们之前已证明羊膜、绒毛膜蜕膜和胎盘中存在PPAR-γ mRNA，且其表达水平在分娩时未发生变化。为评估PPAR-α和-δ亚型是否存在于子宫内组织中，从足月自然阴道分娩的妇女（TSL；n = 15）和分娩前择期剖宫产的妇女（TNL；n = 15）获取胎盘。采用Northern印迹分析评估PPARs的mRNA。使用转染了PPAR反应元件报告构建体（pTK-PPREx3-luc）并用PPAR配体处理的JEG3绒毛膜癌细胞评估PPARs的活性。PPAR-γ特异性配体罗格列酮以浓度依赖性方式诱导PPAR反应元件（PPRE）介导的活性，而PPAR-γ特异性不可逆抑制剂GW9662完全抑制了这种诱导作用。然而，GW9662仅部分抑制15-脱氧-Δ12,14-前列腺素J2（15d-PGJ2）诱导的荧光素酶活性，这表明15d-PGJ2也可能激活其他亚型中的一种。PPAR-α和-δ在羊膜、绒毛膜蜕膜和胎盘绒毛组织中表达。在羊膜中，尽管PPAR-α的表达在分娩时未观察到显著差异，但PPAR-δ的表达显著增加（p < 0.001）。在绒毛膜蜕膜中，PPAR-α的表达随分娩而下降（p < 0.01），而与羊膜中一样，PPAR-δ的表达增加（p < 0.05）。在胎盘中，PPAR-α和-δ的表达均随分娩而增加（p < 0.005）。分娩时观察到的这些变化表明，PPAR表达和功能的调节可能在维持妊娠或启动分娩的机制中发挥作用。
