Factors associated with serum high mobility group box 1 (HMGB1) levels in a general population

Fukami, Ako; Adachi, Hisashi; Yamagishi, Sho‐ichi; Matsui, Takanori; Ueda, Shinichiro; Nakamura, Kazuo; Enomoto, Masaru; Otsuka, Maki; Kumagae, Shun-ichi; Nanjo, Yasuki; Kumagai, Eita; Esaki, Eishi; Murayama, K.; Hirai, Yuji; Imaizumi, Tsutomu

doi:10.1016/j.metabol.2009.05.024

Cited by 44 publications

(33 citation statements)

References 30 publications

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“…In addition, in the present study, the mean (SD) serum sRAGE concentration was 1344.8 (563.9) pg/ml. Although the concentrations of circulating ligands for RAGE were not measured in this study, a previous study of Japanese adult men reported that the concentration of circulating high mobility group box 1, a RAGE ligand, was 1.69 (0.04) ng/ml [21]. As RAGE is known to be a multi-ligand receptor, the potential ligand concentration likely exceeds the sRAGE concentration.…”

Section: Discussionmentioning

confidence: 85%

Higher serum soluble receptor for advanced glycation end product levels and lower prevalence of metabolic syndrome among Japanese adult men: a cross-sectional study

Momma

Niu

Kobayashi

et al. 2014

Diabetol Metab Syndr

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BackgroundAlthough several studies showed that decreased soluble receptor for advanced glycation end products (sRAGE) is associated with metabolic syndrome (MetS), inflammation level has not been considered, even though ligand–RAGE interaction induces inflammation. The objective of the study was to determine the association between sRAGE and MetS among Japanese adult in a cross-sectional survey, taking the level of low grade inflammation into consideration.MethodsSerum soluble RAGE (sRAGE) were measured in 712 men and 176 women aged 30–83 years with serum C-reactive protein (hsCRP) concentration below 3 mg/L. MetS was defined using the criteria of the American Heart Association Scientific Statements of 2009.ResultsAfter multivariable adjustment, among men, higher sRAGE levels were associated with lower odds of MetS as well as central obesity and elevated blood pressure. Comparing the extreme tertiles of sRAGE, odds ratios (95% confidence interval) were 0.58 (0.36–0.95; P for trend = 0.001) for MetS; 0.41 (0.25–0.52; P for trend < 0.001) for central obesity; and 0.45 (0.29–0.70; P for trend < 0.001) for elevated blood pressure. Moreover, participants were categorized according to their median hsCRP and sRAGE values. Men in the higher hsCRP/higher sRAGE category had a 40% lower odds ratio for MetS than those in the higher hsCRP/lower sRAGE category (P = 0.031). Among women, there was no association between sRAGE levels and the prevalence of MetS.ConclusionsHigher circulating RAGE concentrations were associated with lower prevalence of MetS and its components among Japanese men.

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Section: Discussionmentioning

confidence: 85%

Higher serum soluble receptor for advanced glycation end product levels and lower prevalence of metabolic syndrome among Japanese adult men: a cross-sectional study

Momma

Niu

Kobayashi

et al. 2014

Diabetol Metab Syndr

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“…HMGB1 is secreted by preadipocytes and controls inflammation (ie, the secretion of interleukine-6 and monocyte chemotactic protein-1) in adipose tissues through the binding to RAGE (34). In general population sRAGE independently and inversely associated with HMGB1 (35). Herein we showed negative relationship between inflammatory markers (hsCRP, AOPP/Alb) and sRAGE.…”

Section: Discussionmentioning

confidence: 99%

Association between metabolically healthy central obesity in women and levels of soluble receptor for advanced glycation end products, soluble vascular adhesion protein-1, and activity of semicarbazide-sensitive amine oxidase

et al. 2017

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AimTo determine the levels of circulating soluble receptor for advanced glycation end products (sRAGE), as a biomarker of risk of metabolic syndrome and cardiovascular disease development in centrally obese (CO) women considered metabolically healthy (COH) in comparison with those metabolically unhealthy (COU).Methods47 lean healthy, 17 COH (presenting waist-to-height ratio ≥0.5 but not elevated blood pressure, atherogenic lipid profile, and insulin resistance), and 50 COU (CO presenting ≥2 risk factors) women aged 40-45 years were included. Anthropometric characteristics, blood chemistry and hematology data, adipokines, markers of inflammation, sRAGE, soluble vascular adhesion protein-1 (sVAP-1), and the activity of semicarbazide sensitive amine oxidase (SSAO) were determined.ResultsCentral obesity associated with low sRAGE levels (lean healthy: 1503 ± 633 pg/mL; COH: 1103 ± 339 pg/mL, P < 0.05; COU: 1106 ± 367 ng/mL, P < 0.0.1), hyperleptinemia, and elevated markers of inflammation irrespective of the presence or absence of cardiometabolic risk factors. COU women presented high adiponectin levels. SVAP-1 concentrations and the activity of SSAO were similar in all 3 groups.ConclusionCOH women present abnormalities in non-standard markers of cardiometabolic risk (sRAGE, leptin, high sensitive C-reactive protein), supporting the view that there is no healthy pattern of obesity. The clinical impact of our findings for future prognosis of metabolically healthy obese subjects remains to be elucidated in longitudinal studies.

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“…A number of studies have indicated that the level of HMGB1 in samples (e.g., serum, plasma, cerebrospinal fluid, sputum, urine, fecal, and tissue) may be a biomarker of human disease which can be used for detection and diagnosis of disease, prediction of response to therapeutic interventions, and prognosis of outcome. Interestingly, circulating HMGB1 levels have been positively or inversely associated with sRAGE levels, suggesting that sRAGE not only regulates HMGB1 activity, but also eliminates circulating HMGB1 in human disease (Fukami et al, 2009). Currently, ELISA and Western blot have been used to detect HMGB1 in serum, plasma, and body fluid.…”

Section: Hmgb1 Measurements and Significance In Clinical Practicementioning

confidence: 99%

HMGB1 in health and disease

Kang

Chen

Zhang

et al. 2014

Molecular Aspects of Medicine

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828

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Complex genetic and physiological variations as well as environmental factors that drive emergence of chromosomal instability, development of unscheduled cell death, skewed differentiation, and altered metabolism are central to the pathogenesis of human diseases and disorders. Understanding the molecular bases for these processes is important for the development of new diagnostic biomarkers, and for identifying new therapeutic targets. In 1973, a group of non-histone nuclear proteins with high electrophoretic mobility was discovered and termed High-Mobility Group (HMG) proteins. The HMG proteins include three superfamilies termed HMGB, HMGN, and HMGA. High-mobility group box 1 (HMGB1), the most abundant and well-studied HMG protein, senses and coordinates the cellular stress response and plays a critical role not only inside of the cell as a DNA chaperone, chromosome guardian, autophagy sustainer, and protector from apoptotic cell death, but also outside the cell as the prototypic damage associated molecular pattern molecule (DAMP). This DAMP, in conjunction with other factors, thus has cytokine, chemokine, and growth factor activity, orchestrating the inflammatory and immune response. All of these characteristics make HMGB1 a critical molecular target in multiple human diseases including infectious diseases, ischemia, immune disorders, neurodegenerative diseases, metabolic disorders, and cancer. Indeed, a number of emergent strategies have been used to inhibit HMGB1 expression, release, and activity in vitro and in vivo. These include antibodies, peptide inhbitiors, RNAi, anti-coagulants, endogenous hormones, various chemical compounds, HMGB1-receptor and signaling pathway inhibition, artificial DNAs, physical strategies including vagus nerve stimulation and other surgical approaches. Future work further investigating the details of HMGB1 localizationtion, structure, post-translational modification, and identifccation of additional partners will undoubtedly uncover additional secrets regarding HMGB1’s multiple functions.

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Factors associated with serum high mobility group box 1 (HMGB1) levels in a general population

Cited by 44 publications

References 30 publications

Higher serum soluble receptor for advanced glycation end product levels and lower prevalence of metabolic syndrome among Japanese adult men: a cross-sectional study

Higher serum soluble receptor for advanced glycation end product levels and lower prevalence of metabolic syndrome among Japanese adult men: a cross-sectional study

Association between metabolically healthy central obesity in women and levels of soluble receptor for advanced glycation end products, soluble vascular adhesion protein-1, and activity of semicarbazide-sensitive amine oxidase

HMGB1 in health and disease

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