Biomedical Sciences Department, Korea University College of Medicine, Seoul 02841, Republic of Korea.
Central Research Institute, Designed Cells Co., Ltd., Cheongju 28576, Korea.
Endocrinology. 2024 Jul 26;165(9). doi: 10.1210/endocr/bqae095.
Premature rupture of membranes (PROM) is defined as rupture of fetal membranes before the onset of labor. Prolactin (PRL) is secreted by decidual membranes and accumulated significantly in the amniotic fluid during pregnancy. PRL could ameliorate inflammation and collagen degradation in fetal membranes. However, the role of PRL in amniotic membrane is not well characterized. We isolated human amniotic epithelial stem cells (hAESCs) from human fetal membranes to study the effect of PRL on proliferation, migration, and antioxidative stress. Amniotic pore culture technique (APCT) model was constructed to evaluate the tissue regeneration effect in vitro. The potential targets and pathways of PRL acting in amnion via integrated bioinformatic methods. PRL had a dose-dependent effect on hAESCs in vitro. PRL (500 ng/mL) significantly improved the viability of hAESCs and inhibited cell apoptosis, related to the upregulation of CCN2 expression and downregulation of Bax, Caspase 3, and Caspase 8. PRL accelerated migration process in hAESCs via downregulation of MMP2, MMP3, and MMP9. PRL attenuated the cellular damage and mitochondrial dysfunction induced by hydrogen peroxide in hAESCs. PRL accelerated the healing process in the APCT model significantly. The top 10 specific targets (IGF1R, SIRT1, MAP2K1, CASP8, MAPK14, MCL1, NFKB1, HIF1A, MTOR, and HSP90AA1) and signaling pathways (such as HIF signaling pathway) were selected using an integrated bioinformatics approach. PRL improves the viability and antioxidative stress function of hAESCs and the regeneration of ruptured amniotic membranes in vitro. Thus, PRL has great therapeutic potential for prevention and treatment of ruptured membranes.
胎膜早破（PROM）定义为分娩前胎膜破裂。催乳素（PRL）由蜕膜分泌，并在妊娠期间在羊水中大量积累。PRL 可以改善胎膜的炎症和胶原降解。然而，PRL 在羊膜中的作用尚未得到很好的描述。我们从人胎盘中分离出人羊膜上皮干细胞（hAESCs），以研究 PRL 对增殖、迁移和抗氧化应激的影响。采用羊膜孔培养技术（APCT）模型体外评估组织再生效果。通过整合生物信息学方法研究 PRL 作用于羊膜的潜在靶点和途径。PRL 在体外对 hAESCs 具有剂量依赖性作用。PRL（500ng/ml）显著提高了 hAESCs 的活力，抑制了细胞凋亡，与 CCN2 表达上调和 Bax、Caspase 3 和 Caspase 8 下调有关。PRL 通过下调 MMP2、MMP3 和 MMP9 加速 hAESCs 的迁移过程。PRL 减轻了 hAESCs 中过氧化氢引起的细胞损伤和线粒体功能障碍。PRL 显著加速了 APCT 模型中的愈合过程。使用整合生物信息学方法选择了前 10 个特定靶点（IGF1R、SIRT1、MAP2K1、CASP8、MAPK14、MCL1、NFKB1、HIF1A、MTOR 和 HSP90AA1）和信号通路（如 HIF 信号通路）。PRL 提高了 hAESCs 的活力和抗氧化应激功能，以及体外破裂羊膜的再生。因此，PRL 在预防和治疗胎膜早破方面具有很大的治疗潜力。
