High Mobility Group Box-1: A Missing Link between Diabetes and Its Complications

Wu, Han; Chen, Zheng; Xie, Jun; Kang, Lina; Lian, Wang; Xu, Biao

doi:10.1155/2016/3896147

Cited by 43 publications

(53 citation statements)

References 90 publications

(127 reference statements)

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“…Moreover, HMGB1 contributes to cell migration and proliferation, cell differentiation and tissue regeneration [3,20,25], taking part in different pathophysiological processes and diseases, such as sepsis, arthritis, cancer, atherosclerosis, diabetes and cardiovascular diseases [19,[27][28][29][30][31]. HMGB1 is translocated outside the cell in case of cellular damage or cellular death and it was also clearly shown that it can be actively secreted by stimulated immune cells such as monocytes, macrophages, mature dendritic (MD) cells, natural killer (NK) cells and endothelial cells as a result of different stimuli, such as exposure to lipopolysaccharide (LPS), TNF-α, or IL-1β, IFN-γ and tissue injury [3,19,25,[32][33][34]. Furthermore, it has been demonstrated that oxidative stress influences the release of HMGB1 [35].…”

Section: Hmgb1 and Diabetesmentioning

confidence: 99%

“…Interestingly, Lu and colleagues showed that translocation from nucleus to cytoplasm, is mediated by JAK/STAT1 pathway [36], and translocation from cytoplasm to extracellular milieu depends on a mechanism mediated by inflammasome activation during pyroptosis, a form of pro-inflammatory programmed cell death [36]. In diabetes condition, hyperglycemia promotes directly or indirectly, through ROS and AGEs production, the release of HMGB1 [32]. It has been demonstrated that HMGB1 is overexpressed in diabetic patients, compared to non-diabetic [37][38][39].…”

Section: Hmgb1 and Diabetesmentioning

confidence: 99%

“…It is expressed by different cells, including monocytes, macrophages, fibroblasts, smooth muscle cells, endothelial cells and cancers cells, and it plays a pivotal role in diabetes pathogenesis and progression [3]. Binding RAGE, HMGB1 activates CDC42/Rac and mitogen-activated protein kinase (MAPKs) pathways, in particular p38 mitogen-activated protein kinase (p38MAPK), and extracellular signal-regulated kinase (ERK), leading to nuclear translocation of activated nuclear factor-kB (NF-kB) [32]. NF-kB promotes the release of different cytokines (including TNF-α, IL-6, IL-1), growth factors and adhesive molecules responsible for endothelial cells activation, chemotaxis and maturation of immune cells [3,25,32].…”

Section: The Role Of Ragementioning

confidence: 99%

“…Binding RAGE, HMGB1 activates CDC42/Rac and mitogen-activated protein kinase (MAPKs) pathways, in particular p38 mitogen-activated protein kinase (p38MAPK), and extracellular signal-regulated kinase (ERK), leading to nuclear translocation of activated nuclear factor-kB (NF-kB) [32]. NF-kB promotes the release of different cytokines (including TNF-α, IL-6, IL-1), growth factors and adhesive molecules responsible for endothelial cells activation, chemotaxis and maturation of immune cells [3,25,32]. RAGE is also involved in ROS formation, enhancing oxidative stress by NADPH oxidase activation [42].…”

Section: The Role Of Ragementioning

confidence: 99%

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High Mobility Group Box-1 and Diabetes Mellitus Complications: State of the Art and Future Perspectives

Biscetti

Rando

Nardella

et al. 2019

IJMS

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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.

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Section: Hmgb1 and Diabetesmentioning

confidence: 99%

Section: Hmgb1 and Diabetesmentioning

confidence: 99%

Section: The Role Of Ragementioning

confidence: 99%

Section: The Role Of Ragementioning

confidence: 99%

See 2 more Smart Citations

High Mobility Group Box-1 and Diabetes Mellitus Complications: State of the Art and Future Perspectives

Biscetti

Rando

Nardella

et al. 2019

IJMS

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“…The mitogen-activated protein kinase (MAPK) signalling pathways, including extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38 MAPK, are a series of parallel cascades of serine/threonine kinases that are activated by extracellular HMGB1, which also results in the inflammatory response. It is worth mentioning that these inflammatory molecules, in turn, promote additional release of HMGB-1 from cells, resulting in a vicious cycle [8][9][10][11]. GA, also known as Glycyrrhizin, is a triterpenoid triterpene glycoside that is naturally extracted from the roots of licorice plants.…”

Section: Introductionmentioning

confidence: 99%

High Mobility Group Box1 Inhibitor Glycyrrhizic Acid Attenuates Kidney Injury in Streptozotocin-Induced Diabetic Rats

Zhang

Chen

et al. 2017

Kidney Blood Press Res

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Background/Aims: High mobility group box 1 (HMGB1) is an important mediator of the inflammatory response. It has been implicated in the pathogenesis of autoimmune diseases, atherosclerosis, and obesity. However, the effects of HMGB1 on diabetic nephropathy remain unclear. Here, we investigated the potential roles and mechanisms of an HMGB1 inhibitor, glycyrrhizic acid (GA), in renal injury with the streptozotocin (STZ)-induced rat model. Methods: The diabetic rat was generated by intraperitoneal injection of STZ and then treated with the HMGB1 inhibitor GA or saline for 8 weeks. Rats were randomly divided into three groups: the normal control and saline group (Control), the diabetic rats with saline group (Diabetic) and the diabetic rats plus GA group (Diabetic+GA). Peripheral blood was obtained for measurements of blood glucose, TNF-a, IL-6 and IL-1β. The mRNA levels of proinflammatory cytokines (TNF-a, IL-6 and IL-1β), chemokines (MCP-1), intercellular adhesion molecules (ICAM-1) and TGF-β1 in the kidneys were evaluated by quantitative real-time PCR. The protein levels of phosphorylated(p) and total(t) p38 MAPK, JNK, ERK, and NF-κB were measured by western blot. Results: We found that diabetic rats showed obvious renal lesions, an elevated urinary albumin/creatinine ratio (UACR) and increased expression levels of TGF-β1 and Col-IV in the kidneys, accompanied by significantly enhanced expression levels of HMGB1, receptor for advanced glycation end products (RAGE) and toll-like receptor 4 (TLR-4) in the kidney tissue. Furthermore, the GA treatment significantly reduced the UAC levels, ameliorated renal injury, and decreased the TNF-α, 1L-6, IL-1β, MCP-1, ICAM-1, TGF-β1 and Col-IV levels. Importantly, the expression levels of HMGBI, RAGE and TLR4 in the kidney tissues of the diabetic rats were also inhibited by the GA treatment. Furthermore, the GA treatment significantly reduced the phosphorylation levels of ERK and p38 MAPK and suppressed NF-κB translocation from the cytoplasm to the nucleus. Conclusion: Our findings indicate that the HMGB1 inhibitor GA may improve renal injury and inflammatory responses in diabetic rats by regulating RAGE/TLR4-related ERK and p38 MAPK/NF-κB activation.

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PKA regulates HMGB1 through activation of IGFBP-3 and SIRT1 in human retinal endothelial cells cultured in high glucose

2018

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Objective and Design. Inflammation is a key component of a number of diseases, including diabetic retinopathy. We investigated the cellular pathway by which protein kinase A (PKA) inhibited high mobility group box 1 (HMGB1). Methods. Primary human retinal endothelial cells (REC) were grown in normal glucose (5mM) or high glucose (25mM). Cells in high glucose were treated with exchange protein for cAMP 1 (Epac1) and IGFBP-3 siRNA. Additional cells in high glucose were treated with forskolin, a PKA agonist, and Epac1 siRNA. Some cells were treated with a plasmid for insulin-like growth factor binding protein 3 (IGFBP-3) that does not bind IGF-1. Finally, some REC received Ex527, a sirtuin 1 (SIRT1) antagonist, prior to forskolin treatment. Protein analyses were done for HMGB1, Epac1, IGFBP-3, SIRT1, and PKA. Results. PKA inhibited cytoplasmic HMGB1, independent of Epac1 actions. PKA activated IGFBP-3 and SIRT1 to inhibit cytoplasmic HMGB1. High glucose inhibited SIRT1 levels and increased cytoplasmic HMGB1 in REC. Conclusions. PKA requires active IGFBP-3 and SIRT1 to inhibit HMGB1 inflammatory actions in the retina vasculature. Activation of these pathways may offer new targets for therapy development.

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High Mobility Group Box-1: A Missing Link between Diabetes and Its Complications

Cited by 43 publications

References 90 publications

High Mobility Group Box-1 and Diabetes Mellitus Complications: State of the Art and Future Perspectives

High Mobility Group Box-1 and Diabetes Mellitus Complications: State of the Art and Future Perspectives

High Mobility Group Box1 Inhibitor Glycyrrhizic Acid Attenuates Kidney Injury in Streptozotocin-Induced Diabetic Rats

PKA regulates HMGB1 through activation of IGFBP-3 and SIRT1 in human retinal endothelial cells cultured in high glucose

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