Shan Nan, Zhang Xuemei, Xiao Xiaoqiu, Zhang Hua, Chen Ying, Luo Xin, Liu Xiru, Zhuang Baimei, Peng Wei, Qi Hongbo
Department of Obstetrics and Gynecology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People's Republic of China.
Laboratory of Lipid & Glucose Research, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Reprod Sci. 2015 Aug;22(8):969-79. doi: 10.1177/1933719115570913. Epub 2015 Feb 11.
Preeclampsia (PE) is associated with defective placental angiogenesis and poor placentation. Laminins are the main noncollagenous glycoproteins in basement membranes, and laminin α4 (LAMA4) promotes the migration, proliferation, and survival of various cells. The primary purpose of this study is to investigate the role of LAMA4 in human umbilical vein endothelial cells (HUVECs) function during the development of PE. We found expression levels of LAMA4 in human PE placentas were significantly lower compared to the control placentas. The LAMA4 small-interfering RNA transfection and hypoxia-reoxygenation (H/R) intervention reduced the migratory and tube formation abilities of HUVECs. The mitogen-activated protein kinase (MAPK) signaling pathways interacted with LAMA4 expression and H/Rexposure led to MAPK pathways activation in HUVECs. We demonstrated that LAMA4 is very crucial in promoting the functions of endothelial cells. Oxidative stress plays a vital role in controlling expression of LAMA4 through MAPK signaling pathways, which suggests a possible pathological mechanism of PE.
子痫前期（PE）与胎盘血管生成缺陷和胎盘形成不良有关。层粘连蛋白是基底膜中的主要非胶原蛋白糖蛋白，层粘连蛋白α4（LAMA4）可促进各种细胞的迁移、增殖和存活。本研究的主要目的是探讨LAMA4在PE发生发展过程中对人脐静脉内皮细胞（HUVECs）功能的作用。我们发现，与对照胎盘相比，人PE胎盘中LAMA4的表达水平显著降低。LAMA4小干扰RNA转染和缺氧复氧（H/R）干预降低了HUVECs的迁移和管形成能力。丝裂原活化蛋白激酶（MAPK）信号通路与LAMA4表达相互作用，H/R暴露导致HUVECs中MAPK通路激活。我们证明LAMA4在促进内皮细胞功能方面非常关键。氧化应激通过MAPK信号通路在控制LAMA4表达中起重要作用，这提示了PE可能的病理机制。
