Syncytin-1 nonfusogenic activities modulate inflammation and contribute to preeclampsia pathogenesis

Bu, Chaozhi; Wang, Zhiwei; Ren, Yongwei; Chen, Daozhen; Jiang, Shi‐Wen

doi:10.1007/s00018-022-04294-2

Cited by 16 publications

(10 citation statements)

References 123 publications

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“…Although pregnancy is considered a state of low-grade, systemic inflammatory responses [60,61], increased circulatory levels of inflammatory factors including Il1b, Il6, and Tnf-α are associated with adverse pregnancy outcomes, such as PE [62][63][64][65][66]. In addition, inflammatory factors promote the production of antiangiogenic factors sFlt-1 and sEng in placenta [67][68][69]. Some studies have demonstrated that the inhibition of cyclooxygenase and prostaglandin production can relieve placental inflammation, stabilize vascular endothelium, and ultimately alleviate the characterization of PE [70,71].…”

Section: Discussionmentioning

confidence: 99%

Mitochondrial ROS Accumulation Contributes to Maternal Hypertension and Impaired Remodeling of Spiral Artery but Not IUGR in a Rat PE Model Caused by Maternal Glucocorticoid Exposure

et al. 2023

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Increased maternal glucocorticoid levels have been implicated as a risk factor for preeclampsia (PE) development. We found that pregnant rats exposed to dexamethasone (DEX) showed hallmarks of PE features, impaired spiral artery (SA) remodeling, and elevated circulatory levels of sFlt1, sEng IL-1β, and TNFα. Abnormal mitochondrial morphology and mitochondrial dysfunction in placentas occurred in DEX rats. Omics showed that a large spectrum of placental signaling pathways, including oxidative phosphorylation (OXPHOS), energy metabolism, inflammation, and insulin-like growth factor (IGF) system were affected in DEX rats. MitoTEMPO, a mitochondria-targeted antioxidant, alleviated maternal hypertension and renal damage, and improved SA remodeling, uteroplacental blood flow, and the placental vasculature network. It reversed several pathways, including OXPHOS and glutathione pathways. Moreover, DEX-induced impaired functions of human extravillous trophoblasts were associated with excess ROS caused by mitochondrial dysfunction. However, scavenging excess ROS did not improve intrauterine growth retardation (IUGR), and elevated circulatory sFlt1, sEng, IL-1β, and TNFα levels in DEX rats. Our data indicate that excess mitochondrial ROS contributes to trophoblast dysfunction, impaired SA remodeling, reduced uteroplacental blood flow, and maternal hypertension in the DEX-induced PE model, while increased sFlt1 and sEng levels and IUGR might be associated with inflammation and an impaired energy metabolism and IGF system.

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Section: Discussionmentioning

confidence: 99%

Mitochondrial ROS Accumulation Contributes to Maternal Hypertension and Impaired Remodeling of Spiral Artery but Not IUGR in a Rat PE Model Caused by Maternal Glucocorticoid Exposure

et al. 2023

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“…Preeclampsia is usually associated with elevated expression levels of pro-inflammatory cytokines and excessive oxidative stress, leading to abnormal development of placental blood vessels and interstitium [8,9]. Increased levels of inflammation caused by infection is one of the most common factors in PE, which affects the safety of the mother and offspring [9].…”

Section: Discussionmentioning

confidence: 99%

Nicotinamide phosphoribosyltransferase inhibitor is a potential therapeutic target in LPS-induced human trophoblast cell injury

Zhang,

Tang,

Huang

et al. 2023

Trop. J. Pharm Res

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Purpose: To investigate the role of nicotinamide phosphoribosyltransferase (NAMPT) in lipopolysaccharide (LPS)-induced damage in trophoblastic HTR-8/SVneo cells (HTR8 cells), with the aim of ultimately providing new therapeutic targets of preeclampsia (PE).Methods: Trophoblastic HTR-8/SVneo was cultured and treated with LPS to mimic PE in vitro, while FK866, an antagonist of NAMPT, was used to establish an inflammatory model of HTR8 cells. Western blot, enzyme-linked immunosorbent assay (ELISA) and quantitative real-time-polymerase chain reaction (qRT-PCR) were used to evaluate inflammatory response in HTR8 cells, and cell counting kit-8 (CCK8) and oxidative stress kits were performed to quantify cell activity in HTR cells.Results: Compared with the control group, the administration of LPS significantly increased the expression levels of NAMPT in HTR8 cells. FK866 suppressed the expression levels of proinflammatory factors IL-1β, TNF-α and IL-6, and alleviated inflammation by inhibiting NAMPT-mediated NF-κB pathway. The antioxidant effect of FK866 was achieved via activation of antioxidant proteins,catalase (CAT) and glutathione (GSH).Conclusion: FK866 protects HTR8 cells from LPS-induced inflammation and oxidative stress through the inhibition of NAMPT-NF-κB signaling pathway. Thus, NAMPT is a potential therapeutic target for preeclampsia (PE).

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“…Syncytin-1 is involved in the proliferation of cytotrophoblasts through cell cycle [ 28 ], and also mediates the fusion of the villous cytotrophoblast into multinucleated syncytiotrophoblasts [ 36 , 63 , 64 ], the insufficient expression levels of syncytin-1 may lead to defects in the structure and function of the syncytium. In addition, studies have shown that syncytin-1 could also have non-fusogenic activities by participating in the proliferation, differentiation and apoptosis of the trophoblast [ 65 ]. In summary, the expression of syncytin-1 is regulated by methylation, cAMP-PKA-GCM1 signal pathway.…”

Section: The Regulation Mechanisms Of Syncytin-1 In Physiological Pro...mentioning

confidence: 99%

Molecular mechanisms of syncytin-1 in tumors and placental development related diseases

Wang,

Shi,

Bian

et al. 2023

Discov Onc

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Human endogenous retroviruses (HERVs) have evolved from exogenous retroviruses and account for approximately 8% of the human genome. A growing number of findings suggest that the abnormal expression of HERV genes is associated with schizophrenia, multiple sclerosis, endometriosis, breast cancer, bladder cancer and other diseases. HERV-W env (syncytin-1) is a membrane glycoprotein which plays an important role in placental development. It includes embryo implantation, fusion of syncytiotrophoblasts and of fertilized eggs, and immune response. The abnormal expression of syncytin-1 is related to placental development-related diseases such as preeclampsia, infertility, and intrauterine growth restriction, as well as tumors such as neuroblastoma, endometrial cancer, and endometriosis. This review mainly focused on the molecular interactions of syncytin-1 in placental development-related diseases and tumors, to explore whether syncytin-1 can be an emerging biological marker and potential therapeutic target.

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Syncytin-1 nonfusogenic activities modulate inflammation and contribute to preeclampsia pathogenesis

Cited by 16 publications

References 123 publications

Mitochondrial ROS Accumulation Contributes to Maternal Hypertension and Impaired Remodeling of Spiral Artery but Not IUGR in a Rat PE Model Caused by Maternal Glucocorticoid Exposure

Mitochondrial ROS Accumulation Contributes to Maternal Hypertension and Impaired Remodeling of Spiral Artery but Not IUGR in a Rat PE Model Caused by Maternal Glucocorticoid Exposure

Nicotinamide phosphoribosyltransferase inhibitor is a potential therapeutic target in LPS-induced human trophoblast cell injury

Molecular mechanisms of syncytin-1 in tumors and placental development related diseases

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