Medical University of Lodz, Department of Medical Biotechnology, 90-752 Lodz, Poland.
Medical University of Lodz, Department of Cell Cultures and Genomic Analysis, 90-752 Lodz, Poland.
Int J Mol Sci. 2020 Aug 4;21(15):5574. doi: 10.3390/ijms21155574.
Although higher nuclear factor κB (NFκB) expression and activity is observed in preeclamptic placentas, its mechanism of activation is unknown. This is the first study to investigate whether the canonical, non-canonical, or atypical NFκB activation pathways may be responsible for the higher activation of NFκB observed in preeclamptic placentas. The study included 268 cases (130 preeclamptic women and 138 controls). We studied the expression of the genes coding for NFκB activators (NIK, IKKα, IKKβ, and CK2α) and inhibitors (IκBα and IκBβ) using RT-PCR in real time. The RT-PCR results were verified on the protein level using ELISA and Western blot. To determine the efficiency of the pathways, the ratios of activator(s) to one of the inhibitors (IκBα or IκBβ) were calculated for each studied pathway. The preeclamptic placentas demonstrated significantly lower IKKα and CK2α but higher IκBα and IκBβ protein levels. In addition, the calculated activator(s) to inhibitor (IκBα or IκBβ) ratios suggested that all studied pathways might be downregulated in preeclamptic placentas. Our results indicate that preeclamptic placentas may demonstrate mechanisms of NFκB activation other than the canonical, non-canonical, and atypical forms. In these mechanisms, inhibitors of NFκB may play a key role. These observations broaden the existing knowledge regarding the molecular background of preeclampsia development.
虽然在子痫前期胎盘组织中观察到较高的核因子 κB（NFκB）表达和活性，但其激活机制尚不清楚。这是第一项研究，旨在探讨经典、非经典或非典型 NFκB 激活途径是否可能导致子痫前期胎盘组织中观察到的 NFκB 较高激活。该研究共纳入 268 例病例（130 例子痫前期孕妇和 138 例对照）。我们使用实时 RT-PCR 研究了编码 NFκB 激活剂（NIK、IKKα、IKKβ 和 CK2α）和抑制剂（IκBα 和 IκBβ）的基因表达。通过 ELISA 和 Western blot 在蛋白质水平上验证了 RT-PCR 结果。为了确定途径的效率，我们计算了每个研究途径的激活剂（s）与抑制剂之一（IκBα 或 IκBβ）的比值。与对照组相比，子痫前期胎盘组织中 IKKα 和 CK2α 的蛋白水平显著降低，而 IκBα 和 IκBβ 的蛋白水平显著升高。此外，计算出的激活剂（s）与抑制剂（IκBα 或 IκBβ）比值表明，所有研究途径在子痫前期胎盘组织中可能受到下调。我们的结果表明，子痫前期胎盘组织可能表现出不同于经典、非经典和非典型形式的 NFκB 激活机制。在这些机制中，NFκB 的抑制剂可能发挥关键作用。这些观察结果拓宽了我们对子痫前期发展的分子背景的现有认识。
