Significance Of High Mobility Group Box 1 Research Articles

High Mobility Group Box-1 (HMGB1)/microRNA-155 Axis in the Pathogenesis of Type 2 Diabetes Mellitus Associated Periodontitis: A Case Control Study

Aim: To evaluate the role of the high mobility group box-1 (HMGB1)/miR-155 axis in the pathogenesis of stage III/IV periodontitis with and without type 2 diabetes mellitus (T2DM). Materials and Methods: A total of 48 patients were assigned into four groups (12 per group): group 1: systemically and periodontally healthy (PH), group 2: systemically healthy with stage III/IV periodontitis (PD), group 3: PH with T2DM (PH + T2DM), group 4: stage III/IV periodontitis with T2DM, HbA1c ≤ 7 (PD + T2DM). Site-specific plaque index (SS-PI), gingival index (SS-GI), mean probing pocket depth (M-PPD) and clinical attachment loss (M-CAL) were recorded. Gingival tissue samples were analysed for HMGB1 and miR-155 gene expression by real-time polymerase chain reaction. Results: The miR-155 fold change (FC) increased by 10.29, 8.1 and 5.6 times in groups 4, 3 and 2, respectively. Intergroup comparison of miR-155 FC showed a significant difference between the groups ( p < .05). HMGB1 FC increased by 6.5, 5.9 and 5.23 times in groups 4, 2 and 3, respectively, with no significant difference ( p > .05). miR-155 FC is positively and significantly correlated with M-PPD (group 1, 2 and total sample), site-specific plaque score (SS-PS) (group 4) and SS-GI (total sample). miR-155 could discriminate periodontal health from T2DM + PD based on area under the curve 0.82 ( p < .05) with 83.3% sensitivity, 75% specificity, 76.9% positive and 81.8% negative predictive value and 79.2% diagnostic accuracy. Conclusion: miR-155 is significantly upregulated in the diseased periodontium both in the presence and absence of T2DM. Further, miR-155 could be a potential diagnostic biomarker for diabetes-associated PD. However, the significance of HMGB1 and the HMGB1-miR155 axis in the aetiology of diabetes-associated PD is still unclear and warrants additional investigation.

Clinical significance of high-mobility group box-1 (HMGB1) in subjects with type 2 diabetes mellitus (T2DM) combined with chronic obstructive pulmonary disease (COPD).

BackgroundSimple method to predict type 2 diabetes mellitus (T2DM) combined with chronic obstructive pulmonary disease (COPD) is in great need clinically. This study aims to assess the clinical significance of high‐mobility group box‐1 (HMGB1) in predicting T2DM combined with COPD in Chinese patients with T2DM or COPD.MethodsSerum concentrations of glycated hemoglobin (HbA1C), fasting plasma glucose (FPG), fasting insulin (FINS), total cholesterol (TC), triglyceride (TG), low‐density lipoprotein cholesterol (LDL‐c), high‐density lipoprotein cholesterol (HDL‐c), C‐reactive protein (CRP), fibrinogen (FIB), HMGB1, white blood cell count (WBC), neutrophil% (NEU%), and lung function text such as forced expiratory volume 1/forced vital capacity (FEV1/FVC) and forced expiratory volume 1% predicted value (FEV1%pred) were measured in 126 T2DM patients, 118 COPD patients, 112 T2DM combined with COPD patients, and 120 healthy controls. Logistic regression was used to estimate the risk factors for T2DM combined with COPD.ResultsHigh‐mobility group box‐1 elevated in patients with T2DM combined with COPD, significantly higher than other subjects (P < 0.05), and differences in HMGB1 also existed between patients with T2DM or COPD and healthy individuals (P < 0.01). HMGB1 was positively correlated with HOMA‐IR, FBG, and HbA1c (P < 0.01) and negatively correlated with FEV1/FVC and FEV1%pred (P < 0.01). Logistic regression showed that HMGB1 was identified to be independent risk factor for T2DM combined with COPD.ConclusionHigh‐mobility group box‐1 was independent risk factor for T2DM combined with COPD and can be served to predict the occurrence of T2DM combined with COPD.

Glycyrrhizin, a Direct HMGB1 Antagonist, Ameliorates Inflammatory Infiltration in a Model of Autoimmune Thyroiditis via Inhibition of TLR2-HMGB1 Signaling.

High mobility group box-1 (HMGB1), a non-histone protein, plays an important role in autoimmune diseases. However, the significance of HMGB1 in the pathogenesis of autoimmune thyroiditis has not been reported. The purpose of this study was to explore whether HMGB1 participates in the pathogenesis of autoimmune thyroiditis, and whether glycyrrhizin (GL), a direct inhibitor of HMGB1, attenuates the severity of thyroid inflammatory infiltration in a murine model of autoimmune thyroiditis. A total of 80 male NOD.H-2h4 mice were randomly divided into a control or iodine supplement (NaI) group at four weeks of age, and the control group was fed with regular water, whereas the NaI group was supplied with 0.005% sodium iodine water. Another 24 male NOD.H-2h4 mice were also randomized into three groups (eight mice per group) as follows: control, NaI, and GL treatment after iodine supplementation (NaI + GL). The NOD.H-2h4 mice were fed with 0.005% sodium iodide water for eight weeks to enhance autoimmune thyroiditis. After iodine treatment, the mice received intraperitoneal injections of GL for four weeks. The severity of lymphocytic infiltration in the thyroid gland was measured by histopathological studies. The serum levels of HMGB1, tumor necrosis factor alpha, interleukin (IL)-6, IL-1β, and thyroglobulin antibody titers were measured using an enzyme-linked immunosorbent assay. HMGB1 expression was measured by immunohistochemical staining and real-time polymerase chain reaction. TLR2, HMGB1, MyD88, and nuclear transcription factor κB were measured by Western blot. The mRNA expression of HMGB1 was significantly higher at 8 and 16 weeks in the NaI group than it was in the control group. Serum levels of thyroglobulin antibodies, HMGB1, tumor necrosis factor alpha, IL-6, and IL-1β were significantly increased in the NaI group, but they were dramatically attenuated with GL injection. The prevalence of thyroiditis and the infiltration of lymphocytes were significantly decreased in the NaI + GL group. GL administration also significantly reduced the protein expression of TLR2, MyD88, HMGB1 and nuclear transcription factor κB in the thyroid gland and attenuated the severity of thyroiditis. HMGB1 may play a crucial role in autoimmune thyroiditis by causing inflammatory infiltration, thus increasing the severity of autoimmune thyroiditis. GL effectively attenuated thyroiditis in the iodine-induced NOD.H-2h4 mice via a molecular mechanism related to the inhibition of TLR2-HMGB1 signaling.

Clinical and prognostic significance of high-mobility group box-1 in human gliomas.

The objective of this study was to explore the expression and the clinical and prognostic significance of high-mobility group box-1 (HMGB1) in human gliomas. The expression of HMGB1 in 15 samples of normal brain tissue and 65 samples of different-grade glioma tissue was assayed using immunohistochemistry and western blot analysis. The associations between the differences in expression and pathology grades were analyzed statistically. Uni- and multivariate analyses were performed to investigate the prognostic value of HMGB1 expression and its expression levels. The positive rates of HMGB1 expression in normal brain and glioma tissue were 20.0% (3/15) and 76.9% (50/65), respectively. The expression of HMGB1 in glioma tissue was higher than that in normal tissue (P<0.05). The positive rates of HMGB1 expression in low-grade gliomas (LGGs, grades I and II) and high-grade gliomas (HGGs, grades III and IV) were 63.0% (17/27) and 86.8% (33/38), respectively, and the positive rates in HGG were higher than those in LGG (P=0.024). Western blot analysis showed that HMGB1 was also expressed in normal brain tissue. The expression levels in HGG were significantly higher than those in LGG (P<0.001). HMGB1-positive patients had significantly shorter overall survival times compared with HMGB1-negative patients (P=0.026). Increasing levels of HMGB1 expression significantly correlated with reduced survival times when all patients with glioma were considered (P=0.045). In conclusion, HMGB1 positivity and protein expression levels are of significant clinical and prognostic value in human gliomas. Detecting HMGB1 in human gliomas may be useful for assessing the degree of malignancy, and HMGB1 would appear to be a promising target in the clinical management of patients with glioma.

Expression and significance of HMGB1 in esophageal squamous cell carcinoma

Objective: To conduct a preliminary investigation on the expression of the high-mobility group box-1 (HMGB1) protein, and its relationship to metastasis of the lymph nodes and prognosis of patients with esophageal squamous cell carcinoma (ESCC). Methods: Specimens from 72 cases with complete clinical and follow-up data of thoracic ES-CC were collected. Immunohistochemical and statistical methods were used to observe the expressions of HMGB1 and VEGF-C, VEGF-D, LYVE-1 in ESCC. The relationship among the expression of HMGB1, VEGF-C and VEGF-D, micro-lymphatic vessel density (MLD), lymphatic metastasis, as well as between the pathological parameters and prognosis of the ESCC patients were analyzed. Results: There was a high expression of HMGB1 protein in ESCC, and the positive rate of the protein reached 69.44%. However, there was less expression in the normal tissue. The positive rate of HMGB1 expression in the group with lymph node metastasis was significantly higher than in the group without (81.82% vs 58.97%), with a significant difference between the two (P0.05). Moreover, the HMGB1 expression was closely correlated to ESCC staging, expression of VEGF-C and VEGF-D, MLD, as well as the prognosis of the patients (P0.05 or P0.01). At the same time, the VEGF-C and VEGF-D expression were also in close relation with the lymphatic metastasis of ESCC and MLD (P0.05, P0.01) Conclusion: In ESCC, the considerable expression of HMGB1 may promote the lymph- angiogenesis by regulating the expression of VEGF-C and VEGF-D, thus facilitating the lymphatic metastasis and affecting the prognosis. Therefore, HMGB1 may possibly become a major biological marker reflecting the prognosis of ESCC and an important target of anti -lymphangiogenesis in treatment.