Department of Obstetrics, Gynecology and Reproductive Biology, College of Human Medicine, Michigan State University, Grand Rapids, MI 49503, USA.
Int J Mol Sci. 2021 Oct 18;22(20):11229. doi: 10.3390/ijms222011229.
Irisin is a newly discovered exercise-mediated polypeptide hormone. Irisin levels increase during pregnancy however, women with preeclampsia (PE) have significantly lower levels of Irisin compared to women of healthy pregnancies. Even though many studies suggest a role of Irisin in pregnancy, its function in the human placenta is unclear. In the current study, we aimed to understand key roles of Irisin through its ability to protect against apoptosis is the preeclamptic placenta and in ex vivo and in vitro models of hypoxia/re-oxygenation (H/R) injury. Our studies show that Irisin prevents cell death by reducing pro-apoptotic signaling cascades, reducing cleavage of PARP to induce DNA repair pathways and reducing activity of Caspase 3. Irisin caused an increase in the levels of anti-apoptotic BCL2 to pro-apoptotic BAX and reduced ROS levels in an in vitro model of placental ischemia. Furthermore, we show that Irisin treatment acts through the Akt signaling pathway to prevent apoptosis and enhance cell survival. Our findings provide a novel understanding for the anti-apoptotic and pro-survival properties of Irisin in the human placenta under pathological conditions. This work yields new insights into placental development and disease and points towards intervention strategies for placental insufficiencies, such as PE, by protecting and maintaining placental function through inhibiting hypoxic ischemia-induced apoptosis.
鸢尾素是一种新发现的运动介导的多肽激素。怀孕期间鸢尾素水平升高，然而，子痫前期（PE）患者的鸢尾素水平明显低于健康妊娠妇女。尽管许多研究表明鸢尾素有在妊娠中的作用，但它在人胎盘中的功能尚不清楚。在本研究中，我们旨在通过其在预防子痫前期胎盘细胞凋亡中的作用来理解鸢尾素的关键作用，以及在缺氧/复氧（H/R）损伤的离体和体外模型中。我们的研究表明，鸢尾素通过减少促凋亡信号级联反应、减少 PARP 裂解以诱导 DNA 修复途径和减少 Caspase 3 的活性来防止细胞死亡。鸢尾素增加了抗凋亡 BCL2 与促凋亡 BAX 的水平，并降低了体外胎盘缺血模型中的 ROS 水平。此外，我们表明鸢尾素治疗通过 Akt 信号通路起作用，以防止细胞凋亡并增强细胞存活。我们的发现为鸢尾素在病理条件下对人胎盘的抗凋亡和促生存特性提供了新的认识。这项工作为胎盘发育和疾病提供了新的见解，并为通过抑制缺氧缺血诱导的凋亡来保护和维持胎盘功能，以治疗胎盘功能不全（如 PE）提供了干预策略。
