scholarly journals Roles of High Mobility Group Box 1 in Cardiovascular Calcification

2017 ◽  
Vol 42 (2) ◽  
pp. 427-440 ◽  
Author(s):  
Qiang Chen ◽  
Ze-Yang Wang ◽  
Li-Yuan Chen ◽  
Hou-Yuan Hu
Keyword(s):  
Cell Activation ◽  
High Mobility ◽  
Extracellular Vesicle ◽  
High Mobility Group ◽  
Ectopic Calcification ◽  
Cardiac Events ◽  
Calcific Aortic Valve Disease ◽  
Molecular Pattern ◽  
Underlying Mechanisms ◽  
Almost All

Calcific disease of the cardiovascular system, including atherosclerotic calcification, medial calcification in diabetes and calcific aortic valve disease, is an important risk factor for many adverse cardiovascular events such as ischemic cardiac events and subsequent mortality. Although cardiovascular calcification has long been considered to be a passive degenerative occurrence, it is now recognized as an active and highly regulated process that involves osteochondrogenic differentiation, apoptosis and extracellular vesicle release. Nonetheless, despite numerous studies on the pathogenesis of cardiovascular calcification, the underlying mechanisms remain poorly understood. High mobility group box 1 (HMGB1), a nuclear protein bound to chromatin in almost all eukaryotic cells, acts as a damage-associated molecular pattern (DAMP) when released into the extracellular space upon cell activation, injury or death. Moreover, HMGB1 also functions as a bone-active cytokine participating in bone remodeling and ectopic calcification pathogenesis. However, studies on the roles of HMGB1 in promoting cardiovascular calcification are limited to date, and the mechanisms involved are still unclear. In this review, we summarize recent studies investigating the mechanism of cardiovascular calcification and discuss multiple roles of HMGB1 in its development.

The Role of High Mobility Group Box 1 (HMGB1) in Neurodegeneration: A Systematic Review

2022 ◽  
Vol 20 ◽  
Author(s):  
Fathimath Zaha Ikram ◽  
Alina Arulsamy ◽  
Thaarvena Retinasamy ◽  
Mohd. Farooq Shaikh
Keyword(s):  
Systematic Review ◽  
Tissue Injury ◽  
High Mobility ◽  
High Mobility Group ◽  
Hmgb1 Protein ◽  
Toll Like Receptor 4 ◽  
Neuroinflammatory Response ◽  
Molecular Pattern ◽  
Glycation End Products

Background: High mobility group box 1 (HMGB1) protein is a damage-associated molecular pattern (DAMP) molecule that plays an important role in the repair and regeneration of tissue injury. It also acts as a pro-inflammatory cytokine through the activation of toll-like receptor 4 (TLR4) and receptor for advanced glycation end products (RAGE), to elicit the neuroinflammatory response. HMGB1 may aggravate several cellular responses which may lead to pathological inflammation and cellular death. Thus, there have been a considerable amount of research into the pathological role of HMGB1 in diseases. However, whether the mechanism of action of HMGB1 is similar in all neurodegenerative disease pathology remains to be determined. Objective: Therefore, this systematic review aimed to critically evaluate and elucidate the role of HMGB1 in the pathology of neurodegeneration based on the available literature. Methods: A comprehensive literature search was performed on four databases; EMBASE, PubMed, Scopus, and CINAHL Plus. Results: A total of 85 articles were selected for critical appraisal, after subjecting to the inclusion and exclusion criteria in this study. The selected articles revealed that HMGB1 levels were found elevated in most neurodegeneration except in Huntington’s disease and Spinocerebellar ataxia, where the levels were found decreased. This review also showcased that HMGB1 may act on distinctive pathways to elicit its pathological response leading to the various neurodegeneration processes/diseases. Conclusion: While there have been promising findings in HMGB1 intervention research, further studies may still be required before any HMGB1 intervention may be recommended as a therapeutic target for neurodegenerative diseases.

scholarly journals High Mobility Group Box 1 Protein in Cerebral Thromboemboli

2021 ◽  
Vol 22 (20) ◽  
pp. 11276
Author(s):  
Fabian Essig ◽  
Lilith Babilon ◽  
Christoph Vollmuth ◽  
Alexander M. Kollikowski ◽  
Mirko Pham ◽  
...  
Keyword(s):  
Mechanical Thrombectomy ◽  
High Mobility ◽  
Large Vessel ◽  
High Mobility Group ◽  
Neutrophil Extracellular Trap ◽  
Spatial Proximity ◽  
Large Vessel Occlusion ◽  
Vessel Occlusion ◽  
Molecular Pattern ◽  
Hmgb1 Expression

High-mobility group box 1 protein (HMGB1) is a damage-associated molecular pattern (DAMP) involved in neutrophil extracellular trap (NET) formation and thrombosis. NETs are regularly found in cerebral thromboemboli. We here analyzed associated HMGB1 expression in human thromboemboli retrieved via mechanical thrombectomy from 37 stroke patients with large vessel occlusion. HMGB1 was detected in all thromboemboli, accounting for 1.7% (IQR 0.6–6.2%) of the total thromboemboli area and was found to be colocalized with neutrophils and NETs and in spatial proximity to platelets. Correlation analysis revealed that the detection of HMGB1 was strongly related to the number of neutrophils (r = 0.58, p = 0.0002) and platelets (r = 0.51, p = 0.001). Our results demonstrate that HMGB1 is a substantial constituent of thromboemboli causing large vessel occlusion stroke.

High Mobility Group Box 1: An Immune-regulatory Protein

2019 ◽  
Vol 19 (2) ◽  
pp. 100-109 ◽  
Author(s):  
Jingjing Zhao ◽  
Tianle Sun ◽  
Shengdi Wu ◽  
Yufeng Liu
Keyword(s):  
Inflammatory Response ◽  
Transcription Regulation ◽  
Tissue Regeneration ◽  
Cell Nucleus ◽  
Immune Cells ◽  
Inflammatory Diseases ◽  
Regulatory Protein ◽  
High Mobility ◽  
High Mobility Group ◽  
Almost All

High mobility group box 1 (HMGB1) presents in almost all somatic cells as a component of the cell nucleus. It is necessary for transcription regulation during cell development. Recent studies indicate that extracellular HMGB1, coming from necrotic cells or activated immune cells, triggers inflammatory response whereas intracellular HMGB1 controls the balance between autophagy and apoptosis. In addition, reduced HMGB1 can effectively mediate tissue regeneration. HMGB1, therefore, is regarded as a therapeutic target for inflammatory diseases. In this review, we summarized and discussed the immunomodulatory effect of HMGB1.

The Role of High Mobility Group Box 1 Protein in Interleukin-18-Induced Myofibroblastic Transition of Valvular Interstitial Cells

Cardiology ◽  
2016 ◽  
Vol 135 (3) ◽  
pp. 168-178 ◽  
Author(s):  
Bo Wang ◽  
Guangxia Wei ◽  
Baoqing Liu ◽  
Xianming Zhou ◽  
Hua Xiao ◽  
...  
Keyword(s):  
Smooth Muscle Actin ◽  
Plasma Concentrations ◽  
High Mobility ◽  
High Mobility Group ◽  
Valvular Interstitial Cells ◽  
Interleukin 18 ◽  
Calcific Aortic Valve Disease ◽  
Vitro Model

Background: Increased levels of interleukin-18 (IL-18) and high mobility group box 1 protein (HMGB1) have been reported in patients with calcific aortic valve disease (CAVD). However, the role of IL-18 and HMGB1 in the modulation of the valvular interstitial cell (VIC) phenotype remains unclear. We hypothesized that HMGB1 mediates IL-18-induced myofibroblastic transition of VICs. Methods: The expression of IL-18, HMGB1 and α-smooth muscle actin (α-SMA) in human aortic valves was evaluated by immunohistochemical staining, real-time polymerase chain reaction and immunoblotting. Plasma concentrations of IL-18 and HMGB1 were measured using the ELISA kit. Cultured human aortic VICs were used as an in vitro model. Results: Immunohistochemistry and immunoblotting revealed increased levels of IL-18, HMGB1 and α-SMA in calcific valves. Circulating IL-18 and HMGB1 levels were also higher in CAVD patients. In vitro, IL-18 induced upregulation of HMGB1 and α-SMA in VICs. Moreover, IL-18 induced secretion of HMGB1 to the extracellular space and activation of nuclear factor kappa-B (NF-κB). Blockade of NF-κB abrogated the upregulation and release of HMGB1 induced by IL-18. Whereas HMGB1 inhibition attenuated the IL-18-induced expression of α-SMA, HMGB1 enhanced the effect of IL-18. Conclusions: We demonstrated for the first time that both tissue and plasma levels of IL-18 and HMGB1 were increased in patients with CAVD. Mechanically, HMGB1 mediated IL-18-induced VIC myofibroblastic transition.

scholarly journals LPS-induced macrophage HMGB1-loaded extracellular vesicles trigger hepatocyte pyroptosis by activating the NLRP3 inflammasome

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Guozhen Wang ◽  
Siyi Jin ◽  
Weichang Huang ◽  
Yang Li ◽  
Jun Wang ◽  
...  
Keyword(s):  
Cell Death ◽  
Extracellular Vesicles ◽  
Tissue Injury ◽  
High Mobility ◽  
Extracellular Vesicle ◽  
Target Cells ◽  
Hmgb1 Level ◽  
Pyrin Domain ◽  
Molecular Pattern ◽  
Liver Injuries

AbstractExtracellular vesicles (EVs) have emerged as important vectors of intercellular dialogue. High mobility group box protein 1 (HMGB1) is a typical damage-associated molecular pattern (DAMP) molecule, which is cytotoxic and leads to cell death and tissue injury. Whether EVs are involved in the release of HMGB1 in lipopolysaccharide (LPS)-induced acute liver injuries need more investigation. EVs were identified by transmission electron microscopy, nanoparticle tracking analysis (NTA), and western blotting. The co-localization of HMGB1, RAGE (receptor for advanced glycation end-products), EEA1, Rab5, Rab7, Lamp1 and transferrin were detected by confocal microscopy. The interaction of HMGB1 and RAGE were investigated by co-immunoprecipitation. EVs were labeled with the PKH67 and used for uptake experiments. The pyroptotic cell death was determined by FLICA 660-YVAD-FMK. The expression of NLRP3 (NOD-like receptor family pyrin domain containing 3) inflammasomes were analyzed by western-blot or immunohistochemistry. Serum HMGB1, ALT (alanine aminotransferase), AST (aspartate aminotransferase), LDH (lactate dehydrogenase) and MPO (myeloperoxidase) were measured using a commercial kit. The extracellular vesicle HMGB1 was detected in the serums of sepsis patients. Macrophages were found to contribute to HMGB1 release through the EVs. HMGB1-RAGE interactions participated in the loading of HMGB1 into the EVs. These EVs shuttled HMGB1 to target cells by transferrin-mediated endocytosis leading to hepatocyte pyroptosis by the activation of NLRP3 inflammasomes. Moreover, a positive correlation was verified between the sepsis serum EVs-HMGB1 level and clinical liver damage. This finding provides insights for the development of novel diagnostic and therapeutic strategies for acute liver injuries.

NK/iDC interaction results in IL-18 secretion by DCs at the synaptic cleft followed by NK cell activation and release of the DC maturation factor HMGB1

Blood ◽  
2005 ◽  
Vol 106 (2) ◽  
pp. 609-616 ◽  
Author(s):  
Claudia Semino ◽  
Giovanna Angelini ◽  
Alessandro Poggi ◽  
Anna Rubartelli
Keyword(s):  
Nk Cells ◽  
Targeted Delivery ◽  
Cell Activation ◽  
Nk Cell ◽  
Adaptive Immune Response ◽  
High Mobility ◽  
Synaptic Cleft ◽  
Immature Dendritic Cells ◽  
Underlying Mechanisms ◽  
Dc Maturation

Abstract Interaction of natural killer (NK) cells with autologous immature dendritic cells (DCs) results in reciprocal activation; however, the underlying mechanisms are so far elusive. We show here that NK cells trigger immature DCs to polarize and secrete interleukin 18 (IL-18), a cytokine lacking a secretory leader sequence. This occurs through a Ca2+-dependent and tubulin-mediated recruitment of IL-18-containing secretory lysosomes toward the adhering NK cell. Lysosome exocytosis and IL-18 secretion are restricted at the synaptic cleft, thus allowing activation of the interacting NK cells without spreading of the cytokine. In turn, DC-activated NK cells secrete the proinflammatory cytokine high mobility group B1 (HMGB1), which induces DC maturation and protects DCs from lysis. Also HMGB1 is a leaderless cytokine that undergoes regulated secretion. Differently from IL-18, soluble HMGB1 is consistently detected in NK/DC supernatants. These data point to secretion of leaderless cytokines as a key event for the reciprocal activation of NK cells and DCs. DCs initiate NK cell activation by targeted delivery of IL-18, thus instructing NK cells in the absence of adaptive-type cytokines; in turn, activated NK cells release HMGB1, which promotes inflammation and induces DC maturation, thus favoring the onset of the adaptive immune response. (Blood. 2005;106:609-616)

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