SIRT3 deficiency affects the migration, invasion, tube formation and necroptosis of trophoblast and is implicated in the pathogenesis of preeclampsia. (24th March 2022)

• Record Type: Journal Article
• Authors: Yu, Hongbiao; Zhang, Yanping; Liu, Min; Liao, Lingyun; Wei, Xiaohong; Zhou, Rong
• Is Part Of: Placenta. Volume 120(2022)
• Page Start: 1
• Page End: 9
• Publication Date: 2022-03-24
• Subjects: Preeclampsia -- Necroptosis -- Sirtuin 3 -- Trophoblast -- Biological behavior; Placenta -- Periodicals; Reproduction -- Periodicals; Placenta -- Periodicals; Placenta -- Périodiques; Reproduction -- Périodiques; 612.63
• DOI: 10.1016/j.placenta.2022.01.014
• Languages: English
• ISSNs: 0143-4004

Abstract

Abstract: Introduction: Sirtuin 3 (SIRT3) plays a key role in many diseases by regulating cell necroptosis and biological behavior. However, the exact role of SIRT3 in preeclampsia remains unclear. Methods: The expression of SIRT3 and necroptosis biomarkers, including receptor-interacting protein kinase 1 (RIPK1), RIPK3 and phosphorylated mixed lineage kinase domain‐like protein (p-MLKL), in the placentas of 20 healthy pregnancy controls and 20 preeclampsia patients was evaluated by immunofluorescence, quantitative real-time PCR and Western blot. The effect of hypoxia on trophoblast necroptosis was examined in HTR8/SVneo cells. The effects of SIRT3 on the necroptosis, invasion, migration, and tube formation of HTR8/SVneo cells were investigated by transfection with siRNA lentiviruses that silenced or overexpressed SIRT3. Results: The expression of SIRT3 was decreased and the expression of RIPK1, RIPK3 and p-MLKL was increased in placental trophoblasts from preeclampsia patients compared to those from healthy pregnancy controls. Hypoxia increased RIPK1, RIPK3 and p-MLKL expression in HTR8/SVneo cells, while necrostatin-1 pretreatment reduced RIPK1, RIPK3 and p-MLKL expression in HTR8/SVneo cells under hypoxia. SIRT3 silencing increased RIPK1, RIPK3 and p-MLKL expression and inhibited the invasion, migration, and tube formation of HTR8/SVneo cells under hypoxia. SIRT3 overexpression produced the opposite results. Discussion: We report that SIRT3 deficiency may be involved in the pathogenesis of preeclampsia by increasing necroptosis and causing abnormal trophoblastic biological behavior. The underlying mechanisms need further study. Highlights: In placental trophoblasts of preeclampsia patients, necroptosis is increased and SIRT3 expression is decreased. Hypoxia induced necroptosis of HTR8/SVneo. Downregulation of SIRT3 increased necroptosis and inhibited the migration, invasion, and tube formation of HTR8/SVneo. SIRT3 deficiency may contribute to the development of preeclampsia.