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首页> 外文期刊>Journal of cellular physiology. >Irisin induces trophoblast differentiation via AMPK activation in the human placenta
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Irisin induces trophoblast differentiation via AMPK activation in the human placenta

机译：Irisin诱发滋养层分化通过AMPK活化在人类胎盘

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摘要

Irisin, an adipokine, regulates differentiation and phenotype in various cell types including myocytes, adipocytes, and osteoblasts. Circulating irisin concentration increases throughout human pregnancy. In pregnancy disorders such as pre-eclampsia and gestational diabetes mellitus, circulating irisin levels are reduced compared to healthy controls. To date, there are no data on the role and molecular function of irisin in the human placenta or its contribution to pathophysiology. Aberrant trophoblast differentiation is involved in the pathophysiology of pre-eclampsia. The current study aimed to assess the molecular effects of irisin on trophoblast differentiation and function. First-trimester placental explants were cultured and treated with low (10 nM) and high (50 nM) physiological doses of irisin. Treatment with irisin dose-dependently increased both in vitro placental outgrowth (on Matrigel?) and trophoblast cell-cell fusion. Adenosine monophosphate-activated protein kinase (AMPK) signaling, an important regulator of cellular energy home-ostasis that is involved in trophoblast differentiation and pathology, was subsequently investigated. Here, irisin exposure induced placental AMPK activation. To determine the effects of irisin on trophoblast differentiation, two trophoblast-like cell lines, HTR-8/SVneo and BeWo, were treated with irisin and/or a specific AMPK inhibitor (Compound C). Irisin-induced AMPK phosphorylation in HTR-8/SVneo cells. Additionally, as part of the differentiation process, integrin switching from α6 to α1 occurred as well as increased invasiveness. Overall, irisin promoted differentiation in villous and extravillous cell-based models via AMPK pathway activation. These findings provide evidence that exposure to irisin promotes differentiation and improves trophoblast functions in the human placenta that are affected in abnormal placentation.
机译：adipokine Irisin,调节分化并在不同的细胞类型包括表型细胞、脂肪细胞和成骨细胞。循环irisin浓度增加在整个人类怀孕。疾病如先兆子痫、妊娠糖尿病,irisin水平传播减少与健康对照组相比。没有数据和分子作用在人类胎盘irisin或其功能对病理生理学的贡献。滋养层细胞分化是参与子痫前期的病理生理学。研究旨在评估分子的影响irisin滋养层细胞分化和函数。培养和治疗低(10 nM)和高(50 nM)生理剂量的irisin。在与irisin剂量依赖性增加体外胎盘(基底膜基质?)和产物滋养层信息融合。monophosphate-activated蛋白激酶(AMPK)信号,细胞的重要调节器能源home-ostasis参与滋养层细胞分化和病理随后的调查。诱导胎盘AMPK活化。irisin在滋养层的影响分化,两个trophoblast-like细胞系,HTR-8 / SVneo和BeWo irisin对待和/或一个特定的AMPK抑制剂(复合C)。Irisin-induced AMPK磷酸化在HTR-8 / SVneo细胞。分化过程中,整合素转换6αα1发生以及增加侵袭性。分化的绒毛和extravillous通过AMPK途径激活细胞模型。这些发现提供证据表明接触irisin促进分化,改善在人类胎盘滋养层功能在异常胎盘形成的影响。

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