Melatonin regulates trophoblast pyroptosis, invasion and migration in preeclampsia by inhibiting HtrA1 transcription through the microRNA‐520c‐3p/SETD7 axis

Liu, Zhaochun; Chen, Bin; Chang, Jing; Feng, Lulu; Zhao, Xia

doi:10.1111/aji.13523

Cited by 11 publications

(4 citation statements)

References 39 publications

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“…The role of HTRA1 in HTR8/SVneo cell invasion and motility is still a matter of debate. In fact, few studies reported a decreased migration and invasion when HTRA1 was up-regulated by specific plasmids [18,39,40]. Another study reported a significant increase in HTR8/SVneo cell invasion when HTRA1 was overexpressed [41].…”

Section: Discussionmentioning

confidence: 99%

HTRA1 in Placental Cell Models: A Possible Role in Preeclampsia

Tossetta

Fantone

Giannubilo

et al. 2023

CIMB

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The HtrA serine peptidase 1 (HTRA1) is a multidomain secretory protein with serine–protease activity involved in the regulation of many cellular processes in both physiological and pathological conditions. HTRA1 is normally expressed in the human placenta, and its expression is higher in the first trimester compared to the third trimester, suggesting an important role of this serine protease in the early phases of human placenta development. The aim of this study was to evaluate the functional role of HTRA1 in in vitro models of human placenta in order to define the role of this serine protease in preeclampsia (PE). BeWo and HTR8/SVneo cells expressing HTRA1 were used as syncytiotrophoblast and cytotrophoblast models, respectively. Oxidative stress was induced by treating BeWo and HTR8/SVneo cells with H2O2 to mimic PE conditions in order to evaluate its effect on HTRA1 expression. In addition, HTRA1 overexpression and silencing experiments were performed to evaluate the effects on syncytialization, cell mobility, and invasion processes. Our main data showed that oxidative stress significantly increased HTRA1 expression in both BeWo and HTR8/SVneo cells. In addition, we demonstrated that HTRA1 has a pivotal role in cell motility and invasion processes. In particular, HTRA1 overexpression increased while HTRA1 silencing decreased cell motility and invasion in HTR8/SVneo cell model. In conclusion, our results suggest an important role of HTRA1 in regulating extravillous cytotrophoblast invasion and motility during the early stage of placentation in the first trimester of gestation, suggesting a key role of this serine protease in PE onset.

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Section: Discussionmentioning

confidence: 99%

HTRA1 in Placental Cell Models: A Possible Role in Preeclampsia

Tossetta

Fantone

Giannubilo

et al. 2023

CIMB

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“…The downregulated LINC00240 aggravates oxidative stress-induced pyroptosis through increasing miR-155 and reducing Nrf2 expression, and LINC00240 overexpression mitigates the pyroptotic death of trophoblasts (58). Additionally, the lowlyexpressed miR-520c-3p is observed in the placental tissues of PE patients and H/R-treated trophoblasts, and melatonin may suppress trophoblasts pyroptosis via modulating miR-520c-3p/SETD7 axis (93). Taken together, these ncRNAs are expected to be possible therapeutic targets for APS-correlated APOs treatment Recently, trophoblasts pyroptosis has been reported to be modulated by glycolytic enzymes, showing the tightly relation of cellular pyroptosis with metabolic phenotypes.…”

Section: The Role Of Pyroptosis In Trophoblastsmentioning

confidence: 98%

Pyroptosis-triggered pathogenesis: New insights on antiphospholipid syndrome

Tan

Liu

et al. 2023

Front. Immunol.

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APS (antiphospholipid syndrome) is a systematic autoimmune disease presenting with the high levels of aPLs (antiphospholipid antibodies). These autoantibodies are involved in various clinical manifestations, mainly including arterial or venous thrombosis formation, proinflammatory response, and recurrent pregnant loss. Pyroptosis is a form of lytic programmed cell death, and it aggravates autoimmune diseases progression via activating NOD-like receptors, especially the NLRP3 inflammasome and its downstream inflammatory factors IL (interleukin)-1β and IL-18. However, the underlying mechanisms of pyroptosis-induced APS progression remain to be elucidated. ECs (endothelial cells), monocytes, platelets, trophoblasts, and neutrophils are prominent participants in APS development. Of significance, pyroptosis of APS-related cells leads to the excessive release of proinflammatory and prothrombotic factors, which are the primary contributors to APOs (adverse pregnancy outcomes), thrombosis formation, and autoimmune dysfunction in APS. Furthermore, pyroptosis-associated medicines have made encouraging advancements in attenuating inflammation and thrombosis. Given the potential of pyroptosis in regulating APS development, this review would systematically expound the molecular mechanisms of pyroptosis, and elaborate the role of pyroptosis-mediated cellular effects in APS progression. Lastly, the prospective therapeutic approaches for APS would be proposed based on the regulation of pyroptosis.

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“…Excessive apoptosis is closely related to PE, and can be partly reversed by treatments like aspirin, cyclosporine A and resveratrol [ 132 – 134 ]. Pyroptosis in trophoblast cells promotes the occurrence and development of PE [ 135 ]. Some studies have confirmed that pyroptosis occurs in trophoblasts of women with early-onset PE, as evidenced by elevated levels of active caspase-1, GSDMD, IL-1β, and IL-18 [ 42 , 136 , 137 ].…”

Section: Rcd In Different Pregnancy Complicationsmentioning

confidence: 99%

The regulated cell death at the maternal-fetal interface: beneficial or detrimental?

Chen,

Zheng

2024

Cell Death Discov.

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Regulated cell death (RCD) plays a fundamental role in placental development and tissue homeostasis. Placental development relies upon effective implantation and invasion of the maternal decidua by the trophoblast and an immune tolerant environment maintained by various cells at the maternal-fetal interface. Although cell death in the placenta can affect fetal development and even cause pregnancy-related diseases, accumulating evidence has revealed that several regulated cell death were found at the maternal-fetal interface under physiological or pathological conditions, the exact types of cell death and the precise molecular mechanisms remain elusive. In this review, we summarized the apoptosis, necroptosis and autophagy play both promoting and inhibiting roles in the differentiation, invasion of trophoblast, remodeling of the uterine spiral artery and decidualization, whereas ferroptosis and pyroptosis have adverse effects. RCD serves as a mode of communication between different cells to better maintain the maternal-fetal interface microenvironment. Maintaining the balance of RCD at the maternal-fetal interface is of utmost importance for the development of the placenta, establishment of an immune microenvironment, and prevention of pregnancy disorders. In addition, we also revealed an association between abnormal expression of key molecules in different types of RCD and pregnancy-related diseases, which may yield significant insights into the pathogenesis and treatment of pregnancy-related complications.

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Melatonin regulates trophoblast pyroptosis, invasion and migration in preeclampsia by inhibiting HtrA1 transcription through the microRNA‐520c‐3p/SETD7 axis

Cited by 11 publications

References 39 publications

HTRA1 in Placental Cell Models: A Possible Role in Preeclampsia

HTRA1 in Placental Cell Models: A Possible Role in Preeclampsia

Pyroptosis-triggered pathogenesis: New insights on antiphospholipid syndrome

The regulated cell death at the maternal-fetal interface: beneficial or detrimental?

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