Systems Biology of Reproduction Lendulet Research Group, Institute of Enzymology, Research Centre for Natural Sciences, Budapest, Hungary; Department of Morphology and Physiology, Faculty of Health Sciences, Semmelweis University, Budapest, Hungary.
Systems Biology of Reproduction Lendulet Research Group, Institute of Enzymology, Research Centre for Natural Sciences, Budapest, Hungary; First Department of Pathology and Experimental Cancer Research, Semmelweis University, Budapest, Hungary.
Placenta. 2020 Sep 15;99:197-207. doi: 10.1016/j.placenta.2020.05.013. Epub 2020 Jun 22.
Placental Protein 1 (PP1), PP8, and PP22 were isolated from the placenta. Herein, we aimed to identify PP1, PP8, and PP22 proteins and their placental and trophoblastic expression patterns to reveal potential involvement in pregnancy complications.
We analyzed PP1, PP8, and PP22 proteins with LC-MS. We compared the placental behaviors of PP1, PP8, and PP22 to the predominantly placenta-expressed PP5/TFPI-2. Placenta-specificity scores were generated from microarray data. Trophoblasts were isolated from healthy placentas and differentiated; total RNA was isolated and subjected to microarray analysis. We assigned the placentas to the following groups: preterm controls, early-onset preeclampsia, early-onset preeclampsia with HELLP syndrome, term controls, and late-onset preeclampsia. After histopathologic examination, placentas were used for tissue microarray construction, immunostaining with anti-PP1, anti-PP5, anti-PP8, or anti-PP22 antibodies, and immunoscoring.
PP1, PP8, and PP22 were identified as 'nicotinate-nucleotide pyrophosphorylase', 'serpin B6', and 'protein disulfide-isomerase', respectively. Genes encoding PP1, PP8, and PP22 are not predominantly placenta-expressed, in contrast with PP5. PP1, PP8, and PP22 mRNA expression levels did not increase during trophoblast differentiation, in contrast with PP5. PP1, PP8, and PP22 immunostaining were detected primarily in trophoblasts, while PP5 expression was restricted to the syncytiotrophoblast. The PP1 immunoscore was higher in late-onset preeclampsia, while the PP5 immunoscore was higher in early-onset preeclampsia.
PP1, PP8, and PP22 are expressed primarily in trophoblasts but do not have trophoblast-specific regulation or functions. The distinct dysregulation of PP1 and PP5 expression in either late-onset or early-onset preeclampsia reflects different pathophysiological pathways in these preeclampsia subsets.
胎盘蛋白 1（PP1）、PP8 和 PP22 从胎盘分离得到。在此，我们旨在鉴定 PP1、PP8 和 PP22 蛋白及其胎盘和滋养层表达模式，以揭示其在妊娠并发症中的潜在作用。
我们使用 LC-MS 分析 PP1、PP8 和 PP22 蛋白。我们将 PP1、PP8 和 PP22 的胎盘行为与主要在胎盘表达的 PP5/TFPI-2 进行比较。从微阵列数据生成胎盘特异性评分。从健康胎盘分离滋养层细胞并进行分化；分离总 RNA 并进行微阵列分析。我们将胎盘分为以下组：早产对照组、早发型子痫前期组、早发型子痫前期合并 HELLP 综合征组、足月对照组和晚发型子痫前期组。组织病理学检查后，胎盘用于构建组织微阵列，用抗 PP1、抗 PP5、抗 PP8 或抗 PP22 抗体进行免疫染色，并进行免疫评分。
PP1、PP8 和 PP22 分别被鉴定为“烟酸核苷酸焦磷酸化酶”、“丝氨酸蛋白酶抑制剂 B6”和“蛋白质二硫键异构酶”。编码 PP1、PP8 和 PP22 的基因不是主要在胎盘表达，与 PP5 相反。与 PP5 相反，在滋养层分化过程中 PP1、PP8 和 PP22 的 mRNA 表达水平没有增加。PP1、PP8 和 PP22 免疫染色主要在滋养层中检测到，而 PP5 表达局限于合体滋养层。晚期子痫前期的 PP1 免疫评分较高，而早期子痫前期的 PP5 免疫评分较高。
PP1、PP8 和 PP22 主要在滋养层中表达，但没有滋养层特异性调节或功能。PP1 和 PP5 在晚发型或早发型子痫前期中的表达失调不同，反映了这些子痫前期亚组中不同的病理生理途径。
