Department of Medical Microbiology, Immunology and Cell Biology, Southern Illinois University School of Medicine, Springfield, IL 62794-9626, USA.
Placenta. 2009 Oct;30(10):869-75. doi: 10.1016/j.placenta.2009.08.003. Epub 2009 Aug 26.
To determine the mechanism for differential effects of low oxygen tension on human PlGF gene transcription in trophoblast and nontrophoblast cells.
Human PlGF reporter clones and real-time RT-PCR were used to compare the effects of hypoxia on gene transcription in human trophoblast and nontrophoblast cell lines. Overexpression of HIF-1alpha, inhibition of HIF-1 function and biochemical assessments of HIF-1 co-factor interactions were used to characterize hypoxia response mechanisms regulating PlGF transcription.
PlGF transcription is specifically inhibited by low oxygen tension in trophoblast but is induced in some nontrophoblast cells. Overexpression of HIF-1alpha in normoxic cells or inhibition of HIF-1 function in hypoxic cells did not significantly alter transcription patterns of the PlGF gene in either cell type.
These results suggest that transcriptional repression of PlGF gene expression occurs in human trophoblast exposed to low oxygen tension but that PlGF transcription is stimulated in certain hypoxic nontrophoblast cells. However, regulation of PlGF transcription is not mediated by functional HIF-1 activity in either cell type.
确定低氧张力对人胎盘生长因子基因转录在滋养细胞和非滋养细胞中产生差异影响的机制。
利用人胎盘生长因子报告克隆和实时 RT-PCR 比较低氧对人滋养细胞和非滋养细胞系基因转录的影响。过表达 HIF-1α、抑制 HIF-1 功能以及生化评估 HIF-1 共因子相互作用，用于表征调节 PlGF 转录的低氧反应机制。
PlGF 转录在滋养细胞中被低氧张力特异性抑制，但在某些非滋养细胞中被诱导。在常氧细胞中过表达 HIF-1α 或在低氧细胞中抑制 HIF-1 功能，均不能显著改变两种细胞类型中 PlGF 基因的转录模式。
这些结果表明，在暴露于低氧张力的人滋养细胞中 PlGF 基因表达发生转录抑制，但在某些低氧非滋养细胞中 PlGF 转录受到刺激。然而，在这两种细胞类型中，PlGF 转录的调节均不通过功能性 HIF-1 活性介导。
