PEDEGO Research Unit and Medical Research Center Oulu, University of Oulu, Oulu, Finland.
Department of Children and Adolescents, Oulu University Hospital, Oulu, Finland.
Pediatr Res. 2023 Aug;94(2):520-529. doi: 10.1038/s41390-023-02501-9. Epub 2023 Feb 14.
Specific heat shock proteins are associated with pregnancy complications, including spontaneous preterm birth (SPTB). Placental proteomics and whole exome sequencing recently suggested an association between heat shock protein HSPA5 and uncomplicated SPTB. In the present study, we investigated the localization of and possible roles for HSPA5 in SPTB.
Western blot was performed to validate the result from the previously published proteomic analysis. We used qPCR to assess mRNA expression of genes and immunohistochemistry and immunoelectron microscopy to examine localization of HSPA5 in placental tissue. We silenced the HSPA5 gene in the HTR8/SVneo human trophoblast cell line to investigate possible functions of HSPA5.
HSPA5 was upregulated in placentas from SPTBs compared to spontaneous term births. We did not observe upregulation of HSPA5 mRNA in placental samples. The protein was localized in placental trophoblast in both spontaneous preterm and term placentas. Gene silencing of HSPA5 in human trophoblast cell culture affected the inflammatory response and decreased the expression of several proinflammatory genes.
We suggest that upregulation of HSPA5 in the placenta is associated with spontaneous preterm labor. HSPA5 may promote the inflammatory response and alter the anti-inflammatory state of the placenta which could eventually lead to premature labor.
We validated upregulation of HSPA5 in placentas from spontaneous preterm birth. HSPA5 was not upregulated at transcriptional level which suggests that it may be regulated post-translationally. Silencing HSPA5 in a human trophoblast-derived cell line suggested that HSPA5 promotes expression of proinflammatory cytokines. The emerging inflammation could lead to spontaneous preterm labor. Identifying inflammatory pathways and factors associated with spontaneous preterm birth increases knowledge of the molecular mechanisms of premature labor. This could provide cues to predict imminent premature labor and lead to information about how to safely maintain pregnancies.
特定的热休克蛋白与妊娠并发症有关，包括自发性早产（SPTB）。胎盘蛋白质组学和全外显子测序最近表明热休克蛋白 HSPA5 与无并发症的 SPTB 之间存在关联。在本研究中，我们研究了 HSPA5 在 SPTB 中的定位和可能作用。
进行 Western blot 以验证之前发表的蛋白质组学分析的结果。我们使用 qPCR 评估基因的 mRNA 表达，并用免疫组织化学和免疫电镜检查 HSPA5 在胎盘组织中的定位。我们在 HTR8/SVneo 人滋养细胞系中沉默 HSPA5 基因，以研究 HSPA5 的可能功能。
与自发性足月分娩相比，SPTB 的胎盘组织中 HSPA5 上调。我们未观察到胎盘样本中 HSPA5 mRNA 的上调。该蛋白在自发性早产和足月胎盘中的胎盘滋养层中均有定位。在人滋养细胞培养物中沉默 HSPA5 基因会影响炎症反应并降低几种促炎基因的表达。
我们认为胎盘中 HSPA5 的上调与自发性早产有关。HSPA5 可能促进炎症反应并改变胎盘的抗炎状态，最终导致早产。
我们验证了 HSPA5 在自发性早产胎盘中的上调。HSPA5 在转录水平上没有上调，这表明它可能在翻译后受到调控。在人滋养细胞衍生细胞系中沉默 HSPA5 表明 HSPA5 促进促炎细胞因子的表达。新出现的炎症可能导致自发性早产。识别与自发性早产相关的炎症途径和因素增加了对早产分子机制的认识。这可以提供预测即将发生的早产的线索，并提供有关如何安全维持妊娠的信息。
