PEDEGO Research Unit and Medical Research Center Oulu, University of Oulu, Oulu, Finland.
Department of Children and Adolescents, Oulu University Hospital, Oulu, Finland.
Sci Rep. 2021 Aug 24;11(1):17115. doi: 10.1038/s41598-021-96374-9.
Heat shock proteins are involved in the response to stress including activation of the immune response. Elevated circulating heat shock proteins are associated with spontaneous preterm birth (SPTB). Intracellular heat shock proteins act as multifunctional molecular chaperones that regulate activity of nuclear hormone receptors. Since SPTB has a significant genetic predisposition, our objective was to identify genetic and transcriptomic evidence of heat shock proteins and nuclear hormone receptors that may affect risk for SPTB. We investigated all 97 genes encoding members of the heat shock protein families and all 49 genes encoding nuclear hormone receptors for their potential role in SPTB susceptibility. We used multiple genetic and genomic datasets including genome-wide association studies (GWASs), whole-exome sequencing (WES), and placental transcriptomics to identify SPTB predisposing factors from the mother, infant, and placenta. There were multiple associations of heat shock protein and nuclear hormone receptor genes with SPTB. Several orthogonal datasets supported roles for SEC63, HSPA1L, SACS, RORA, and AR in susceptibility to SPTB. We propose that suppression of specific heat shock proteins promotes maintenance of pregnancy, whereas activation of specific heat shock protein mediated signaling may disturb maternal-fetal tolerance and promote labor.
热休克蛋白参与应激反应，包括免疫反应的激活。循环中升高的热休克蛋白与自发性早产（SPTB）有关。细胞内热休克蛋白作为多功能分子伴侣，调节核激素受体的活性。由于 SPTB 具有明显的遗传倾向，我们的目标是确定热休克蛋白和核激素受体的遗传和转录组证据，这些证据可能影响 SPTB 的风险。我们研究了编码热休克蛋白家族成员的所有 97 个基因和编码核激素受体的所有 49 个基因，以确定它们在 SPTB 易感性中的潜在作用。我们使用了多种遗传和基因组数据集，包括全基因组关联研究（GWAS）、全外显子测序（WES）和胎盘转录组学，从母亲、婴儿和胎盘识别 SPTB 的易感因素。热休克蛋白和核激素受体基因与 SPTB 有多种关联。几个正交数据集支持 SEC63、HSPA1L、SACS、RORA 和 AR 基因在 SPTB 易感性中的作用。我们提出，特定热休克蛋白的抑制可能促进妊娠的维持，而特定热休克蛋白介导的信号的激活可能会破坏母体-胎儿耐受并促进分娩。
