HMGB1/RAGE Axis Mediates the Apoptosis, Invasion, Autophay, and Angiogenesis of the Renal Cell Carcinoma [Corrigendum]
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[This corrects the article DOI: 10.2147/OTT.S167197.].Keywords:
HMGB1
RAGE
High mobility group protein box1 (HMGB1) and its receptor—receptor for advanced glycation end products (RAGE) are pivotal factors in the development and progression of many types of tumor, but the role of HMGB1-RAGE axis in hepatocellular carcinoma (HCC) especially its effects on metastasis and recurrence remains obscure. Here, we report the role of HMGB1-RAGE axis in the biological behaviors of HCC cell lines and the underlying molecular mechanism. We show that the expressions of HMGB1, RAGE, and extracellular HMGB1 increase consistently according to cell metastasis potentials, while the concentration of soluble form of RAGE (sRAGE) is inversely related to metastasis potential of HCC cells. Furthermore, our data show that rhHMGB1 promotes cellular proliferation, migration, and invasion, and increases the level of nuclear factor kappa B (NF-κB), while administrations of HMGB1-siRNA, RAGE-siRNA, anti-HMGB1 neutralizing antibody, anti-RAGE neutralizing antibody, and sRAGE inhibit cellular proliferation, migration, and invasion. Moreover, we also demonstrate that the expression of NF-кB is inhibited by knockdown of HMGB1 or RAGE. Collectively, these data demonstrate that HMGB1 activates RAGE signaling pathways and induces NF-кB activation to promote cellular proliferation, invasion, and metastasis, in HCC cell lines. Taken together, HMGB1-RAGE axis may become a potential target in HCC therapy.
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Inflammation plays important roles in the pathogenesis of coxsackievirus B3 (CVB3)-induced acute viral myocarditis (AVMC). Ethyl pyruvate (EP) has been shown to be an anti-inflammatory agent. High mobility group box 1 (HMGB1)/receptor for advanced glycation end product (RAGE)/nuclear factor (NF)-ΚB pathway has close relation with inflammatory responses. Here, we investigated the effects of EP on CVB3-induced AVMC and potential mechanisms. The mice with AVMC were treated with EP (40 or 80 mg/kg/day) from day 5 to day 7 post-infection. EP significantly decreased the mortality of mice with AVMC. H&E staining and immunohistochemistry for HMGB1 demonstrated less inflammatory lesions and fewer abnormal location of HMGB1 in the hearts of AVMC mice receiving EP. Immuoblot showed that EP significantly inhibited the levels of HMGB1, RAGE, phospho(p)-NF-ΚB and p-I-ΚBα, and raised I-ΚBα expression in the hearts of AVMC mice. Furthermore, real-time PCR and Elisa displayed decreased levels of HMGB1, TNF-α, IL-1β, IL-17 and increased levels of IL-10 in the hearts and serum of AVMC mice treated with EP. Our findings suggest that EP protects against CVB3-induced AVMC that is associated with inhibition of HMGB1/RAGE/NF-ΚB pathway.
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Viral Myocarditis
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Coxsackievirus
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Damage-associated molecular patterns (DAMP) and pattern recognition receptors might play a role in the pathogenesis of primary sclerosing cholangitis (PSC). The receptor for advanced glycation end products (RAGE) and its ligand High Mobility Group Box Protein 1 (HMGB1), a nuclear protein with proinflammatory properties, are part of this endogenous system. This study aims to analyze the influence of the HMGB1 and RAGE inflammatory pathway in PSC.
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Primary Sclerosing Cholangitis
Proinflammatory cytokine
Pathogenesis
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HMGB1 (high Mobility Group Box 1) protein is released by nuclear after that binds to DNA. HMGB1 can also be secreted from cells, it can bind receptor for advanced glycation end products (RAGE) that inflammatory receptor. Interaction between HMGB1 and RAGE causes upregulation of NF‐kB that leads to increased production of cytokines. Ethyl pyruvate (EP) is the ethyl ester of pyruvic acid. In recent research, EP has shown HMGB1 inhibitory effecting in many inflammation‐related diseases through pathway inhibition. In this study, we measured that expression of HMGB1 mRNA and proteins stimulated by LPS in presence of ethyl pyruvate (EP) or other inflammatory stimulants was measured as RT‐qPCR and immunoblotting analysis in BMDMs. Furthermore, levels of cytokine in the supernatant of BMDM stimulated by LPS in presence of EP or other inflammatory stimulants or mouse serum were measured by ELISA. Here in we found that EP inhibits HMGB1 pathway leading to reduced RAGE expression and NF‐κB activation. Moreover, we demonstrated EP reduced HMGB1 in serum levels of mice. Our results suggested that EP is effective inhibitors of HMGB1/RAGE signaling pathway, offering a novel potential therapeutic approach to patients and HMGB1 has been proposed as a target for inflammatory disease. Support or Funding Information ACKNOWLEDGEMENTS This work was supported by the NRF grant funded by the Korea government (MSIP) 2019R1I1A2A01064237.
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Abstract RAGE stands for R eceptor of A dvanced Gl ycation E ndproducts. The two main topics discussed are (1) the nature of RAGE signaling and (2) its role in cardiovascular disease. RAGE may occur in membrane‐bound form or in secretory form. RAGE signaling involves multiple ligands: (1) several AGEs (2) amyloid β pecursor protein ( APP ), (3) high mobility group box 1 ( HMGB1 ), (4) S100A4 , (5) S100A8/A9 , and (6) S100A12 , which are calcium‐binding proteins, and (7) S100B , a glial‐derived protein. RAGE ligands and various diseases involving RAGE signaling are summarized in tabular form. © 2013 Wiley Periodicals, Inc.
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Dendritic cells (DC) are key components of innate and adaptive immune responses. Plasmacytoid DC (PDC) are a specialized DC subset that produce high amounts of type I interferons in response to microbes. High mobility group box 1 protein (HMGB1) is an abundant nuclear protein, which acts as a potent pro-inflammatory factor when released extracellularly. We show that HMGB1 leaves the nucleus of maturing PDC following TLR9 activation, and that PDC express on the plasma membrane the best-characterized receptor for HMGB1, RAGE. Maturation and type I IFN secretion of PDC is hindered when the HMGB1/RAGE pathway is disrupted. These results reveal HMGB1 and RAGE as the first known autocrine loop modulating the maturation of PDC, and suggest that antagonists of HMGB1/RAGE might have therapeutic potential for the treatment of systemic human diseases.
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Advanced glycation end-product
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Abstract Aims High mobility group box‐1 (HMGB1) is one of the damage‐associated molecular patterns produced by stress and induces inflammatory responses mediated by receptors of advanced glycation end‐products (RAGE) on the cell surface. Meanwhile, soluble RAGE (sRAGE) exhibits an anti‐inflammatory effect by capturing HMGB1. Animal models have shown upregulation of HMGB1 and RAGE in the brain or blood, suggesting the involvement of these proteins in depression pathophysiology. However, there have been no reports using blood from depressed patients, nor ones focusing on HMGB1 and sRAGE changes associated with treatment and their relationship to depressive symptoms. Methods Serum HMGB1 and sRAGE concentrations were measured by enzyme‐linked immunosorbent assay in a group of patients with severe major depressive disorder (MDD) (11 males and 14 females) who required treatment with electroconvulsive therapy (ECT), and also in a group of 25 age‐ and gender‐matched healthy subjects. HMGB1 and sRAGE concentrations were also measured before and after a course of ECT. Depressive symptoms were assessed using the Hamilton Rating Scale for Depression (HAMD). Results There was no significant difference in HMGB1 and sRAGE concentrations in the MDD group compared to healthy subjects. Although ECT significantly improved depressive symptoms, there was no significant change in HMGB1 and sRAGE concentrations before and after treatment. There was also no significant correlation between HMGB1 and sRAGE concentrations and the HAMD total score or subitem scores. Conclusion There were no changes in HMGB1 and sRAGE in the peripheral blood of severely depressed patients, and concentrations had no relationship with symptoms or ECT.
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Advanced glycation end-product
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HMGB1
RAGE
Advanced glycation end-product
High-mobility group
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Objective To investigate the effect of high-mobility group box protein1(HMGB1) on the expression of TNF-α and its mechanism in 16 HBE in vitro. Methods groups with different HMGB1(0, 100, 500,2 000 ng / m L) concentration was set; RAGE antagonizing groups were as control, HMGB1-2000 ng, anti-RAGE and anti-RAGE+HMGB1. The changes of TNF-α mRNA and secretion were determined by quantitative PCR and ELISA.RAGE protein level was measured by western blotting. Results HMGB1 intervention and TNF-α expression of16 HBE presented a positive dose-dependent relationship. Thechanges of RAGE was HMGB1 positively concentration dependent. In comparison with HMGB1 2 000 ng / m L group, anti-RAGE+HMGB1showed a remarkable reduction of TNF-α secretion. Conclusion In vitro, HMGB1 increases TNF-α expression in 16 HBE with a dose-dependent manner through RAGE.
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