Destruction in maternal-fetal interface of URSA patients via the increase of the HMGB1-RAGE/TLR2/TLR4-NF-κB signaling pathway

Zou, Huijuan; Yin, Jiaqian; Zhang, Zhiguo; Xiang, Hui-Xian; Wang, Jing; Zhu, Damin; Xu, Xiaofeng; Cao, Yunxia

doi:10.1016/j.lfs.2020.117543

Cited by 25 publications

(28 citation statements)

References 36 publications

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“…In further support of the importance of HMGB1 in pregnancy maintenance, HMGB1 maternal plasma concentrations are increased in URSA patients which can activate the RAGE, TLR2, or TLR4 receptors leading to the activation of NF‐κB (Figure 1C). However, HMGB1 plasma levels can be reduced with treatment of the commonly used anti‐inflammatory drug, aspirin 11 . This is notable as few reports describe any manipulation of HMGB1 levels or downstream consequences in the context pregnancy.…”

Section: The Role Of Hmgb1 Throughout Gestationmentioning

confidence: 99%

“…This is notable as few reports describe any manipulation of HMGB1 levels or downstream consequences in the context pregnancy. Although aspirin is not typically recommended for use during pregnancy, one of the exceptions for this is for recurrent pregnancy loss 11 . Further strong evidence to support the importance of the correct levels of HMGB1 during the beginning of pregnancy comes from the demonstration that recombinant HMGB1 administered into the uterine horn of pregnant rats leads to pregnancy failure 8 .…”

Section: The Role Of Hmgb1 Throughout Gestationmentioning

confidence: 99%

“…In support of this strategy, some studies have suggested that HMGB1 be used as a biomarker in maternal serum for chorioamionitis, 40 APS, 34 placenta inflammation, 29 and PE/HDP 14,76 . HMGB1 may also be a useful biomarker for identifying and monitoring the severity of pregnancy‐related diseases, such as GDM 26 and URSA 11 …”

Section: Hmgb1 As a Biomarker Or Therapeutic Target For Pregnancy Commentioning

confidence: 99%

“…These studies had designed their approach to inhibit other targets, but they were also seen to affect the expression and function of HMGB1. Some HMGB1 inhibitors found to treat pregnancy-related pathologies include glycyrrhizin 74 and sodium tanshinone IIA 23 for PE, and aspirin for URSA 11 Indeed, the HMGB1 inhibitor glycyrrhizic acid (GA) decreased the permeability of HUVEC cells induced by hypoxic trophoblasts 74 and reduced cytokine production in fetal membranes treated with GA. 39 Additionally, HMGB1 release from hypoxic trophoblasts was targeted with the novel drug sodium tanshinone IIA (STS) to reduce HUVEC injury, 23 whereas aspirin reduced the levels of HMGB1 within the plasma of URSA patients. shown to directly bind to HMGB1 and reduce cytokine activity while having minimal effects to nuclear function.…”

Section: Hmg B1 a S A B I Omarker Or Ther Apeuti C Targ E T For Prementioning

confidence: 99%

“…HMGB1 also plays an important role in uterine decidualization by mediating the expression of key stromal cell markers that induce the proliferation and differentiation of uterine stromal cells 9 . Although the inflammatory response mediated by HMGB1 in the early stages is critical for pregnancy success, excessive HMGB1 levels within the uterine cavity 8 and expression within the placenta 10,11 have been shown to lead to pregnancy loss. Therefore, this suggests that there is an optimal level, and perhaps a critical window, where HMGB1 expression is needed to promote the initial stages of pregnancy.…”

Section: Introductionmentioning

confidence: 99%

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High‐mobility group box 1 is a driver of inflammation throughout pregnancy

Saito-Reis

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Ing

et al. 2020

American J Rep Immunol

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A proinflammatory response driven by high‐mobility group box 1 (HMGB1) is important for the success of both the early stages of pregnancy and parturition initiation. However, the tight regulation of HMGB1 within these two stages is critical, as increased HMGB1 can manifest into pregnancy‐related pathologies. Although during the early stages of pregnancy HMGB1 is critical for the development and implantation of the embryo, and uterine decidualization, high levels within the uterine cavity have been linked to pregnancy failure. In addition, chronic inflammation, resultant from increased HMGB1 within the maternal circulation and gestational tissues, also increases the risk for preterm labor, preterm birth, or infant mortality. Due to the link between HMGB1 and several pregnancy pathologies, the possibility of leveraging HMGB1 as a biomarker has been assessed. However, data are limited that demonstrate how known HMGB1 inhibitors could reduce inflammation within pregnancy. Thus, further research is warranted to improve our understanding of the potential of HMGB1 as a therapeutic target to reduce inflammation within pregnancy. This review aims to describe what is understood about the role of HMGB1 that drives inflammation throughout pregnancy and highlight its potential as a biomarker and therapeutic target within this context.

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Section: The Role Of Hmgb1 Throughout Gestationmentioning

confidence: 99%

Section: The Role Of Hmgb1 Throughout Gestationmentioning

confidence: 99%

Section: Hmgb1 As a Biomarker Or Therapeutic Target For Pregnancy Commentioning

confidence: 99%

Section: Hmg B1 a S A B I Omarker Or Ther Apeuti C Targ E T For Prementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

High‐mobility group box 1 is a driver of inflammation throughout pregnancy

Saito-Reis

Padron

Ing

et al. 2020

American J Rep Immunol

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Upregulated serum granulysin levels in women with antiphospholipid antibody‐associated recurrent miscarriage are downregulated by heparin treatment

Ichikawa

Negishi

Kasano

et al. 2022

Reprod Medicine & Biology

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Purpose Granulysin is a cytotoxic protein that simultaneously activates innate and cellular immunity. The authors aimed to evaluate whether granulysin is associated with the antiphospholipid antibody syndrome and whether heparin changes the granulysin levels. Methods A cohort study was performed with women with antiphospholipid antibody‐positive recurrent pregnancy loss (RPL). The authors examined granulysin levels under RPL and evaluated the changes in serum granulysin levels before and 1 week after the commencement of heparin treatment. Results Serum granulysin levels before heparin treatment were significantly higher in women who tested positive for one or more types of antiphospholipid antibodies (2.75 ± 1.03 vs. 2.44 ± 0.69, p = 0.0341 by Welch's t test), particularly anti‐phosphatidylethanolamine antibodies (IgG: 2.98 ± 1.09 vs. 2.51 ± 0.86, p = 0.0013; IgM: 2.85 ± 1.09 vs. 2.47 ± 0.77, p = 0.0024 by Welch's t test). After heparin treatment for 1 week, serum granulysin levels were significantly reduced ( p = 0.0017 by the paired t test). The miscarriage rate was significantly higher in women whose serum granulysin levels were not reduced by heparin treatment ( p = 0.0086 by Fisher's exact probability test). Conclusion The results suggest that heparin may reduce the incidence of miscarriage by suppressing serum granulysin levels.

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High-mobility group box 1 (HMGB1) in COVID-19: extrapolation of dangerous liaisons

et al. 2022

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High-mobility group box 1 (HMGB1), a multifunctional nuclear protein, exists mainly within the nucleus of all mammal eukaryotic cells. It is actively secreted by the necrotic cells as a response to the inflammatory signaling pathway. HMGB1 binds to receptor ligands as RAGE, and TLR and becomes a pro-inflammatory cytokine with a robust capacity to trigger inflammatory response. It is a critical mediator of the pathogenesis of systemic inflammation in numerous inflammatory disorders. Release of HMGB1 is associated with different viral infections and strongly participates in the regulation of viral replication cycles. In COVID-19 era, high HMGB1 serum levels were observed in COVID-19 patients and linked with the disease severity, development of cytokine storm (CS), acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). SARS-CoV-2-induced cytolytic effect may encourage release of HMGB1 due to nuclear damage. Besides, HMGB1 activates release of pro-inflammatory cytokines from immune cells and up-regulation of angiotensin I-converting enzyme 2 (ACE2). Therefore, targeting of the HMGB1 pathway by anti-HMGB1 agents, such as heparin, resveratrol and metformin, may decrease COVID-19 severity. HMGB1 signaling pathway has noteworthy role in the pathogenesis of SARS-CoV-2 infections and linked with development of ALI and ARDS in COVID-19 patients. Different endogenous and exogenous agents may affect release and activation of HMGB1 pathway. Targeting of HMGB1-mediated TLR2/TLR4, RAGE and MAPK signaling, might be a new promising drug candidate against development of ALI and/or ARDS in severely affected COVID-19 patients.

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Destruction in maternal-fetal interface of URSA patients via the increase of the HMGB1-RAGE/TLR2/TLR4-NF-κB signaling pathway

Cited by 25 publications

References 36 publications

High‐mobility group box 1 is a driver of inflammation throughout pregnancy

High‐mobility group box 1 is a driver of inflammation throughout pregnancy

Upregulated serum granulysin levels in women with antiphospholipid antibody‐associated recurrent miscarriage are downregulated by heparin treatment

High-mobility group box 1 (HMGB1) in COVID-19: extrapolation of dangerous liaisons

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