Zhang Juzuo, Peng Xuan, Yuan Anwen, Xie Yang, Yang Qing, Xue Liqun
Department of Clinic Veterinary Medicine, College of Veterinary Medicine, Hunan Agricultural University, Changsha, Hunan 410128, P.R. China.
Mol Med Rep. 2017 Sep;16(3):2636-2644. doi: 10.3892/mmr.2017.6903. Epub 2017 Jun 30.
Peroxisome proliferator-activated receptor (PPAR) γ has been reported to be implicated in placentation in mice. Previous studies have demonstrated that PPARγ is also expressed in porcine placenta, primarily localized in vascular endothelial cells (VECs). The present study aimed to investigate the roles of PPARγ during porcine placental angiogenesis and examine the molecular mechanisms involved in its actions. VECs were incubated with the PPARγ agonist rosiglitazone and the antagonist T0070907, and their angiogenic potential was evaluated using cellular impedance, wound healing and tube formation assays. Reverse transcription‑quantitative polymerase chain reaction was used to assess the mRNA expression levels of angiogenic factors, including hypoxia‑inducible factors (HIFs), vascular endothelial growth factor (VEGF) isoforms, VEGF receptors (VEGFRs) and angiopoietins (Angs). The results demonstrated that the adhesive, proliferative and migratory capabilities of VECs were potentiated by rosiglitazone and suppressed by T0070907. Notably, tube formation was invariably promoted during PPARγ activation and blockade. The mRNA expression levels of HIF1α, HIF2α, VEGFR2, VEGF188 and Ang‑1 were revealed to be upregulated following treatment of VECs with rosiglitazone, whereas they were downregulated following treatment with T0070907. However, the mRNA expression levels of placental growth factor and VEGF120 were consistently downregulated following PPARγ activation and blockade, whereas VEGF164 mRNA levels remained unaltered. The results of the present study suggested that PPARγ may mediate porcine placental angiogenesis, by interfering with HIF‑, VEGF‑ and angiopoietin‑mediated signaling pathways.
据报道,过氧化物酶体增殖物激活受体(PPAR)γ与小鼠胎盘形成有关。先前的研究表明,PPARγ也在猪胎盘中表达,主要定位于血管内皮细胞(VECs)。本研究旨在探讨PPARγ在猪胎盘血管生成过程中的作用,并研究其作用的分子机制。将VECs与PPARγ激动剂罗格列酮和拮抗剂T0070907一起孵育,并使用细胞阻抗、伤口愈合和管形成试验评估它们的血管生成潜力。采用逆转录定量聚合酶链反应评估血管生成因子的mRNA表达水平,这些因子包括缺氧诱导因子(HIFs)、血管内皮生长因子(VEGF)异构体、VEGF受体(VEGFRs)和血管生成素(Angs)。结果表明,罗格列酮可增强VECs的黏附、增殖和迁移能力,而T0070907则抑制这些能力。值得注意的是,在PPARγ激活和阻断过程中,管形成总是受到促进。在用罗格列酮处理VECs后,HIF1α、HIF2α、VEGFR2、VEGF188和Ang-1的mRNA表达水平上调,而在用T0070907处理后则下调。然而,在PPARγ激活和阻断后,胎盘生长因子和VEGF120的mRNA表达水平持续下调,而VEGF164的mRNA水平保持不变。本研究结果表明,PPARγ可能通过干扰HIF、VEGF和血管生成素介导的信号通路来介导猪胎盘血管生成。