2. Academic Validation
  3. Mechanism of neutrophil extracellular traps generation and their role in trophoblasts apoptosis in gestational diabetes mellitus

Mechanism of neutrophil extracellular traps generation and their role in trophoblasts apoptosis in gestational diabetes mellitus

  • Cell Signal. 2021 Dec:88:110168. doi: 10.1016/j.cellsig.2021.110168.
Di Shen 1,  Yuan Lu 2,  Guangzhen Li 3,  Min Hu 2,  Shanling Li 4,  Hui Ju 4,  Meihua Zhang 5,  Xietong Wang 6
Affiliations

Affiliations

  • 1 Department of Obstetrics and Gynaecology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, 324 Jingwu Street, Jinan, Shandong 250021, China; Department of Obstetrics and Gynaecology, Maternal and Child Health Care Hospital of Shandong Provincial, Cheeloo College of Medicine, Shandong University, 238 Jingshi East Road, Jinan, Shandong 250014, China.
  • 2 Department of Obstetrics and Gynaecology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, 324 Jingwu Street, Jinan, Shandong 250021, China.
  • 3 Department of General Surgery, Qilu Hospital of Shandong University, 107 Wenhua West Road, 251000, Jinan, China.
  • 4 Department of Obstetrics and Gynaecology, Maternal and Child Health Care Hospital of Shandong Provincial, Cheeloo College of Medicine, Shandong University, 238 Jingshi East Road, Jinan, Shandong 250014, China.
  • 5 The Laboratory of Placenta-Related Diseases, Key Laboratory of Birth Regulation and Control Technology of National Health Commission of China, 238 Jingshi East Road, Jinan, Shandong 250014, China.
  • 6 Department of Obstetrics and Gynaecology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, 324 Jingwu Street, Jinan, Shandong 250021, China; Department of Obstetrics and Gynaecology, Maternal and Child Health Care Hospital of Shandong Provincial, Cheeloo College of Medicine, Shandong University, 238 Jingshi East Road, Jinan, Shandong 250014, China; The Laboratory of Placenta-Related Diseases, Key Laboratory of Birth Regulation and Control Technology of National Health Commission of China, 238 Jingshi East Road, Jinan, Shandong 250014, China. Electronic address: [email protected].
PMID: 34634453 DOI: 10.1016/j.cellsig.2021.110168
Abstract

Gestational diabetes mellitus (GDM) is a metabolic syndrome occurring in pregnant women and increases the risk of placental dysplasia. Neutrophil extracellular traps (NETs) may play a critical role in placental dysplasia. NETosis (neutrophil cell death by NET release) depends on NADPH/ROS pathway. In view of the Adiponectin which is widely believed to be reduced in GDM patients suppresses NADPH Oxidase and ROS generation of neutrophil. We speculate that increased NET release is associated with hypoadiponectinemia. Trophoblast Apoptosis is significantly increased in GDM patients, but it is not clear whether NETs promotes cell Apoptosis. This study aims to reveal the mechanism of Neutrophil Extracellular Traps generation and their role in trophoblast Apoptosis in Gestational Diabetes Mellitus. We investigated the generation of NETs by cell-free DNA (cf-DNA) quantification, live-cell imaging, and Reactive Oxygen Species (ROS) measurement. ERK1/2 and p38 MAPK signalling pathway proteins were detected by western blotting. The Cell Counting Kit-8 (CCK-8) assay, flow cytometry, and western blotting were performed to explore the effects of NETs on trophoblast Apoptosis. We found that Adiponectin inhibited NET release by suppressing ROS production, and p38 MAPK and ERK1/2 proteins were involved in the process. Further, NETs promoted trophoblast Apoptosis by activating the ROS-dependent mitochondrial pathway, which is mediated by ERK1/2 signalling. The current study demonstrated that hypoadiponectinemia is the cause of NETs formation and NETs promoting trophoblast Apoptosis.

Keywords

Adiponectin; Apoptosis; Gestational diabetes mellitus; Neutrophil extracellular traps; Trophoblast.

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