Nesfatin-1 Promotes Proliferation, Migration and Invasion of HTR-8/SVneo Trophoblast Cells and Inhibits Oxidative Stress
- PDF / 14,089,993 Bytes
- 12 Pages / 595.276 x 790.866 pts Page_size
- 93 Downloads / 194 Views
REPRODUCTIVE EPIDEMIOLOGY: ORIGINAL ARTICLE
Nesfatin-1 Promotes Proliferation, Migration and Invasion of HTR-8/SVneo Trophoblast Cells and Inhibits Oxidative Stress via Activation of PI3K/AKT/mTOR and AKT/GSK3β Pathway Tingting Li 1 & Sumei Wei 1 & Conghong Fan 1 & Dongmei Tang 1 & Dan Luo 1 Received: 4 June 2020 / Accepted: 16 September 2020 # Society for Reproductive Investigation 2020
Abstract Preeclampsia (PE) is a leading cause of perinatal and maternal mortality. Considering that Nesfatin-1 was reported to be downregulated in serum of PE patients, we aimed to explore the functional role of Nesfatin-1 in trophoblast cells. Cell transfection was conducted to overexpress or inhibit Nesfatin-1, and its expression was measured by quantitative PCR. Cell proliferation, migration, and invasion abilities were determined employing CCK-8, flow cytometry, wound-healing, and transwell assays. Immunofluorescence assay was performed to detect E-cadherin and vimentin. ROS, MDA, and SOD levels were measured using their corresponding commercial kits. Western blot was used to identify the expression of vital kinases in PI3K/AKT/mTOR or GSK3β pathway and invasion-related proteins in trophoblast cells. Nesfatin-1 knockdown significantly suppressed proliferation, migration, and invasion and increased cell arrest in G1 phase, as well as downregulated expressions of MMP2/9 in HTR-8/SVneo cells. Besides, Nesfatin-1 knockdown promoted the expression of E-cadherin and reduced the expression of vimentin. Additionally, the levels of ROS, MDA, and SOD were elevated upon Nesfatin-1 knockdown. On the contrary, Nesfatin-1 overexpression exerted the opposite effects. Nesfatin-1 promoted the activation of PI3K/AKT/mTOR or GSK3β pathway, blocking of which reversed the promotive effects on trophoblast invasion and the inhibitory effects on oxidative stress of Nesfatin-1 in HTR-8/SVneo cells. In short, this study revealed that Nesfatin-1 promoted trophoblast cell proliferation, migration, invasion, and EMT and suppressed oxidative stress by activating PI3K/AKT/mTOR and AKT/GSK3β signaling pathway, laying the foundation for the development of therapeutic strategy for PE by targeting Nesfatin-1. Keywords Nesfatin-1 . Trophoblast invasion . Oxidative stress . AKT
Introduction Preeclampsia (PE) is a disease among pregnant women characterized by high maternal blood pressure, proteinuria (24-h quantitative urine protein ≥ 2 g), and edema following 20 weeks of gestation, threatening maternal and fetal health [1]. The morbidity of PE in China has achieved 2.4~4.2%, which still fluctuates greatly in economic less-developed regions due to the lack of prevention and treatment [2]. PE is associated with intrauterine growth restriction (IUGR), placental abruption, fetal
* Dan Luo [email protected] 1
Department of Gynaecology and Obstetrics, Chengdu Women’s and Children’s Central Hospital, School of Medicine, University of Electronic Science and Technology of China, NO. 1617 Riyue Avenue, Qingyang District, Chengdu 611731, Sichuan, China
neurotubule mal
Data Loading...
