High Mobility Group Box-1 (HMGB1): A Potential Target in Therapeutics

2019 ◽  
Vol 20 (14) ◽  
pp. 1474-1485 ◽  
Author(s):  
Eyaldeva C. Vijayakumar ◽  
Lokesh Kumar Bhatt ◽  
Kedar S. Prabhavalkar
Keyword(s):  
Myocardial Infarction ◽  
Vagus Nerve Stimulation ◽  
Nuclear Protein ◽  
Therapeutic Potential ◽  
High Mobility ◽  
Dna Binding Protein ◽  
High Mobility Group ◽  
Eukaryotic Cells ◽  
Hmgb1 Protein

High mobility group box-1 (HMGB1) mainly belongs to the non-histone DNA-binding protein. It has been studied as a nuclear protein that is present in eukaryotic cells. From the HMG family, HMGB1 protein has been focused particularly for its pivotal role in several pathologies. HMGB-1 is considered as an essential facilitator in diseases such as sepsis, collagen disease, atherosclerosis, cancers, arthritis, acute lung injury, epilepsy, myocardial infarction, and local and systemic inflammation. Modulation of HMGB1 levels in the human body provides a way in the management of these diseases. Various strategies, such as HMGB1-receptor antagonists, inhibitors of its signalling pathway, antibodies, RNA inhibitors, vagus nerve stimulation etc. have been used to inhibit expression, release or activity of HMGB1. This review encompasses the role of HMGB1 in various pathologies and discusses its therapeutic potential in these pathologies.

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 and Diabetes Mellitus Complications: State of the Art and Future Perspectives

2019 ◽  
Vol 20 (24) ◽  
pp. 6258 ◽  
Author(s):  
Biscetti ◽  
Rando ◽  
Nardella ◽  
Cecchini ◽  
Pecorini ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Central Nervous System ◽  
Nervous System ◽  
Nuclear Protein ◽  
State Of The Art ◽  
High Mobility ◽  
High Mobility Group ◽  
Future Perspectives ◽  
Vascular Bed

Diabetes mellitus (DM) is an endemic disease, with growing health and social costs. The complications of diabetes can affect potentially all parts of the human body, from the heart to the kidneys, peripheral and central nervous system, and the vascular bed. Although many mechanisms have been studied, not all players responsible for these complications have been defined yet. High Mobility Group Box-1 (HMGB1) is a non-histone nuclear protein that has been implicated in many pathological processes, from sepsis to ischemia. The purpose of this review is to take stock of all the most recent data available on the role of HMGB1 in the complications of DM.

scholarly journals Anabolic Properties of High Mobility Group Box Protein-1 in Human Periodontal Ligament CellsIn Vitro

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Michael Wolf ◽  
Stefan Lossdörfer ◽  
Piero Römer ◽  
Rogerio Bastos Craveiro ◽  
James Deschner ◽  
...  
Keyword(s):  
Periodontal Ligament ◽  
Tooth Movement ◽  
Therapeutic Potential ◽  
Marker Gene ◽  
Orthodontic Tooth Movement ◽  
High Mobility ◽  
High Mobility Group ◽  
Nodule Formation ◽  
Hmgb1 Protein ◽  
Pdl Cells

High mobility group box protein-1 (HMGB1) is mainly recognized as a chemoattractant for macrophages in the initial phase of host response to pathogenic stimuli. However, recent findings provide evidence for anabolic properties in terms of enhanced proliferation, migration, and support of wound healing capacity of mesenchymal cells suggesting a dual role of the cytokine in the regulation of immune response and subsequent regenerative processes. Here, we examined potential anabolic effects of HMGB1 on human periodontal ligament (PDL) cells in the regulation of periodontal remodelling, for example, during orthodontic tooth movement. Preconfluent human PDL cells (hPDL) were exposed to HMGB1 protein and the influence on proliferation, migration, osteogenic differentiation, and biomineralization was determined by MTS assay, real time PCR, immunofluorescence cytochemistry, ELISA, and von Kossa staining. HMGB1 protein increased hPDL cell proliferation, migration, osteoblastic marker gene expression, and protein production as well as mineralized nodule formation significantly. The present findings support the dual character of HMGB1 with anabolic therapeutic potential that might support the reestablishment of the structural and functional integrity of the periodontium following periodontal trauma such as orthodontic tooth movement.

Role of High Mobility Group Box1 in Pathogenesis of Hepatitis C Virus induced Hepatocellular Carcinoma

2020 ◽  
Vol EJMM29 (4) ◽  
pp. 135-141
Author(s):  
Nouran E. Samra ◽  
Shahira El-Etreby ◽  
Rasha H. El-Mahdy ◽  
Samah S. El-Kazzaz ◽  
Nariman M. El-Nashar
Keyword(s):  
Hepatocellular Carcinoma ◽  
Immune Response ◽  
Nuclear Dna ◽  
Inflammatory Responses ◽  
High Mobility ◽  
Dna Binding Protein ◽  
High Mobility Group ◽  
Over Expression ◽  
Different Types

Hepatocellular carcinoma "HCC" is a leading cause of cancer mortality worldwide. High-mobility group box 1 "HMGB1" is a nuclear DNA-binding protein which involved in DNA stability, programmed cell death, immune response and inflammatory responses in HCV and HCC. Its over expression was revealed in HCC and different types of human cancers.

High Mobility Group Box-1 Protein and Interleukin 33 Expression in Allergic Rhinitis

ORL ◽  
2022 ◽  
pp. 1-9
Author(s):  
Nongping Zhong ◽  
Qing Luo ◽  
Xiaoyan Huang ◽  
Jieqing Yu ◽  
Jing Ye ◽  
...  
Keyword(s):  
Allergic Rhinitis ◽  
Epithelial Cells ◽  
Nasal Mucosa ◽  
High Mobility ◽  
Normal Group ◽  
High Mobility Group ◽  
Hmgb1 Protein ◽  
Significant Difference

<b><i>Background:</i></b> Allergic rhinitis (AR) is characterized by an inflammatory reaction. High mobility group box 1 (HMGB1) protein and interleukin (IL)-33 are damage-associated molecular pattern molecules and have many characteristics similar to pro-inflammatory cytokines. However, the role of IL-33 and HMGB1 in AR remains unclear. The aim of this study is to explore the role of HMGB1 and IL-33 in AR. <b><i>Methods:</i></b> Twenty patients with AR (AR group) and 10 normal controls (normal group) were enrolled in this study. HMGB1 and IL-33 expression were analyzed by immunohistochemistry in epithelial cells of the inferior turbinate mucosa samples. Then, the human nasal mucosa epithelial cells (HNECs) were cultured in vitro, and the house dust mite allergen (Derp1) was used to stimulate the cells. Quantitative real-time PCR and ELISA assay were performed to detect HMGB1 and IL-33 expression in HNECs. <b><i>Results:</i></b> The expression of HMGB1 and IL-33 in the nasal mucosa was higher in the AR group than in the normal group, with a statistically significant difference (<i>p</i> &#x3c; 0.05). In HNECs of AR, the expression of both HMGB1 and IL-33 in stimulated groups was higher than that in non-stimulated groups. The differences were statistically significant (<i>p</i> &#x3c; 0.05). In addition, they increased gradually with the prolonging time and the concentration of the added Derp1. <b><i>Conclusions:</i></b> The expression of HMGB1 and IL-33 were both increased in AR. HMGB1 and IL-33 may have a close relationship in AR.

scholarly journals High Mobility Group Box 1 Protein Induction byMycobacterium BovisBCG

2007 ◽  
Vol 2007 ◽  
pp. 1-8 ◽  
Author(s):  
Péter Hofner ◽  
György Seprényi ◽  
András Miczák ◽  
Krisztina Buzás ◽  
Zsófia Gyulai ◽  
...  
Keyword(s):  
Mycobacterium Bovis ◽  
In Vitro Model ◽  
Nuclear Protein ◽  
High Mobility ◽  
High Mobility Group ◽  
Pathophysiological Role ◽  
Vitro Model

High mobility group box 1 protein (HMGB1), a nuclear protein, is a critical cytokine that mediates the response to infection, injury, and inflammation. The aim of our study was to elaborate a reliable in vitro model to investigate whetherMycobacterium bovisBCG is able to induce HMGB1 secretion from the monocytic U-937 cells. Western blot technique was applied for the detection of HMGB1 from supernatants of cells, following induction withMycobacterium bovisBCG. Densitometric analysis revealed higher concentrations of HMGB1 in cell supernatants stimulated with BCG than in the supernatants of the control, nonstimulated cells. Further quantitation of the secreted HMGB1 was performed by ELISA. The BCG strain resulted in a higher amount of secreted HMGB1 (450±44 ng/mL) than that of LPS (84±12 ng/mL) orStaphylococcus aureus(150±14 ng/mL). BCG and Phorbol−12-myristate−13acetate (PMA), added together, resulted in the highest HMGB1 secretion (645±125 ng/mL). The translocation of the HMGB1 towards the cytoplasm following infection of cells with BCG was demonstrated by immunofluorescence examinations. Conclusion: Our pilot experiments draw attention to the HMGB1 inducing ability ofMycobacterium bovis. Assesment of the pathophysiological role of this late cytokine in mycobacterial infections demands further in vitro and in vivo examinations.

High mobility group box 1 (HMGB1) protein in Multiple Sclerosis (MS): Mechanisms and therapeutic potential

Life Sciences ◽  
2019 ◽  
Vol 238 ◽  
pp. 116924 ◽  
Author(s):  
Yam Nath Paudel ◽  
Efthalia Angelopoulou ◽  
Bhuvan K C ◽  
Christina Piperi ◽  
Iekhsan Othman
Keyword(s):  
Multiple Sclerosis ◽  
Therapeutic Potential ◽  
High Mobility ◽  
High Mobility Group ◽  
Hmgb1 Protein

scholarly journals Early release of high mobility group box nuclear protein 1 after severe trauma in humans: role of injury severity and tissue hypoperfusion

Critical Care ◽  
2009 ◽  
Vol 13 (6) ◽  
pp. R174 ◽  
Author(s):  
Mitchell J Cohen ◽  
Karim Brohi ◽  
Carolyn S Calfee ◽  
Pamela Rahn ◽  
Brian B Chesebro ◽  
...  
Keyword(s):  
Injury Severity ◽  
Nuclear Protein ◽  
High Mobility ◽  
Severe Trauma ◽  
High Mobility Group ◽  
Early Release ◽  
Tissue Hypoperfusion

scholarly journals The Role of High-Mobility Group Box-1 and Its Crosstalk with Microbiome in Rheumatoid Arthritis

2017 ◽  
Vol 2017 ◽  
pp. 1-11 ◽  
Author(s):  
Federico Biscetti ◽  
Andrea Flex ◽  
Stefano Alivernini ◽  
Barbara Tolusso ◽  
Elisa Gremese ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Autoimmune Disease ◽  
Nuclear Protein ◽  
High Mobility ◽  
Cell Types ◽  
High Mobility Group ◽  
Present Review ◽  
Number Of Patients ◽  
Almost All

Rheumatoid arthritis (RA) is a chronic, definitely disabling, and potentially severe autoimmune disease. Although an increasing number of patients are affected, a key treatment for all patients has not been discovered. High-mobility group box-1 (HMGB1) is a nuclear protein passively and actively released by almost all cell types after several stimuli. HMGB1 is involved in RA pathogenesis, but a convincing explanation about its role and possible modulation in RA is still lacking. Microbiome and its homeostasis are altered in patients with RA, and the microbiota restoration has been proposed to patients with RA. The purpose of the present review is to analyze the available evidences regarding HMGB1 and microbiome roles in RA and the possible implications of the crosstalk between the nuclear protein and microbiome in understanding and possibly treating patients affected by this harmful condition.

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