Molecular insights into the multifaceted functions and therapeutic targeting of high mobility group box 1 in metabolic diseases

Tao, Zhipeng; Helms, My N.; Leach, Benjamin C. B.; Wu, Xu

doi:10.1111/jcmm.17448

Cited by 11 publications

(7 citation statements)

References 61 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Despite several detrimental factors that can stimulate inflammatory response through diverse pathways mediated by HMGB1, the most important one of the pathways is characterized by the activation of NF-kB. Our results are consistent with the previous study that the inhibition of HMGB1 blocks the TLR4/NF-κB mediated inflammatory response ( Tao et al, 2022 ). Our study indicated that GLC may play an important role in the inhibition of this positive feedback from multiple targets, which is a complicated process that needs further study.…”

Section: Discussionsupporting

confidence: 93%

Periplaneta americana extract alleviates steatohepatitis in a mouse model by modulating HMGB1-mediated inflammatory response

Xiao

Gao

et al. 2022

Front. Pharmacol.

View full text Add to dashboard Cite

Alcoholic abuse and obesity are the most common lifestyle implications of chronic liver injury, and always act synergistically to increase the risk of mortality. Periplaneta americana has a long history of being applied in medicine, including wound healing, antitumor, antibacterial, antiviral, antifibrotic, and cardiomyocyte-protecting. Ganlong capsule (GLC), a natural prescription drug extracted from Periplaneta americana, has been widely used in HBV-related symptoms. However, the anti-steatohepatitis efficacy and mechanisms of GLC have not yet been characterized. Here, we found the protective effect of GLC on the development of hepatic steatosis, oxidative stress, and inflammation in vivo under alcohol exposure combined with a high-fat and high-cholesterol diet (HFHC). Consistently, GLC exhibited a hepatoprotective property by preventing hepatocytes from oxidative stress injury and lipid accumulation in vitro. In addition, it exerted an anti-inflammation characteristic by reducing macrophage recruitment and decreasing the expression of pro-inflammatory genes in vivo and in vitro. Mechanically, GLC serum, isolated from GLC-treated mice, reduced extracellular high-mobility group box 1 (HMGB1) of dying hepatocytes; and suppressed subsequent M1 polarization of macrophages in the co-culture system. Furthermore, GLC serum inhibited inflammatory response via suppressing the HMGB1 release and blocking the downstream TLR4/NF-kB pathway. Collectively, GLC alleviates steatohepatitis induced by alcohol consumption and obesity through inhibition of the HMGB1-mediated inflammatory cascade. GLC might be a therapeutic candidate for the treatment of steatohepatitis developed by alcohol abuse and metabolic disorders.

show abstract

Section: Discussionsupporting

confidence: 93%

Periplaneta americana extract alleviates steatohepatitis in a mouse model by modulating HMGB1-mediated inflammatory response

Xiao

Gao

et al. 2022

Front. Pharmacol.

View full text Add to dashboard Cite

show abstract

“…The pro-inflammatory effect of HMGB1 is mainly due to its structural characteristics and derived cellular biological effects ( 9 ). A variety of receptors play a role in HMGB1 signaling, including receptors for advanced non-enzymatic glycation end products (RAGEs) and members of the Toll-like receptors (TLRs) ( 10 ). TLRs bind to RAGEs to amplify the inflammatory response, an important mechanism that promotes atherosclerosis ( 11 ), and HMGB1 is the only known receptor with the highest affinity.…”

Section: Introductionmentioning

confidence: 99%

The clinical significance of serum HMGB1 in patients with lower extremity arteriosclerosis obliterans after interventional vascular restenosis

Yang

Zhang²

2023

Front. Surg.

View full text Add to dashboard Cite

ObjectiveThis study explored the correlation between serum HMGB1 levels and postoperative vascular restenosis in patients with lower extremity arteriosclerosis obliterans (LEASO).MethodsA total of 362 patients LEASO who received vascular intervention were recruited in this study. Serum HMGB1 levels were measured by enzyme-linked immunosorbent assay. Logistic regression analysis was used to identify the influencing factors associated with vascular restenosis. The R procedure was used to create nomogram model. Receiver operating characteristic (ROC) analysis was used to determine the predictive value of serum HMGB1 and nomogram model for vascular restenosis.ResultsOf the 362 LEASO patients included, 103 (28.45%) developed restenosis within 6 months of postoperative follow-up. Postoperative HMGB1 levels were significantly higher in patients with restenosis compared to those with non-restenosis. Postoperative HMGB1 levels were significantly and positively correlated with the severity of postoperative restenosis (r = 0.819). The AUC of postoperative HMGB1 for the diagnosis of postoperative restenosis was 0.758 (95% CI: 0.703–0.812), with a sensitivity and specificity of 56.31% and 82.24%, respectively. Multivariate logistic regression analysis showed that diabetes, smoking, regular postoperative medication, increased fibrinogen, decreased red blood cells, increased hs-CRP, and increased postoperative HMGB1 were independently associated with postoperative restenosis in patients with LEASO. The C-index of the nomogram prediction model constructed based on the seven influencing factors mentioned above was 0.918. The nomogram model was significantly more predictive of postoperative restenosis in LEASO patients compared with a single postoperative HMGB1 (AUC: 0.918, 95% CI: 0.757–0.934).ConclusionPostoperative serum HMGB1 is an independent risk factor associated with postoperative vascular restenosis in patients with LEASO, and a novel nomogram model based on postoperative serum HMGB1 combined with clinical characteristics may help to accurately predict the risk of postoperative restenosis in patients with LEASO.

show abstract

“…Численні дослідження [8,11,16,22,27] показали, що NF-κB є як фактором, активація якого призводить до виділення амфотерину у позаклітинний простір, так і важливою ланкою сигнального шляху, що активується цим білком після його взаємодії з відповідними рецепторами. Активація NF-κB індукує продукцію та вивільнення багатьох прозапальних медіаторів, що визначає надзвичайно важливу роль цього транскрипційного фактора у розвитку запалення та імунній відповіді.…”

Section: шляхи виділення Hmgb1 механізми дії інгібіториunclassified

“…Крім NF-κB позаклітинний HMGB1 регулює передачу сигналів й через інші шляхи, серед яких MAPK і PI3K [27]. Наприклад, активуючи сигнальний шлях TLR4/MyD88/ NF-κB/p65, позаклітинний HMGB1 може сприя ти пошкодженню ендотеліальних клітин гломерулярного апарату нирок під час вовчакового нефриту [28].…”

Section: шляхи виділення Hmgb1 механізми дії інгібіториunclassified

“…HMGB1 бере участь у патогенезі метаболічних захворювань, таких як діабет і пов'язаних з ним ускладнень. Зокрема, у тканині печінки щурів з діабетом взаємодія HMGB1 і TLR4 супроводжується активацією сигнальних шляхів MAPK (p38, ERK, JNK), NFκB-p65 і JAK1/STAT3, що посилює розвиток системного запалення [27]. При гострому ураженні легень, індукованому ЛПС, було виявлено активацію HMGB1-опосередкованих шляхів TLR4/NF-κB та PI3K/ Akt/mTOR [29].…”

Section: шляхи виділення Hmgb1 механізми дії інгібіториunclassified

See 1 more Smart Citation

Multifunctional Activity of Nuclear Protein Amphoterin and Its Role in Endotoxemia

Kondratska,

Grushka,

Veshko

et al. 2023

Fiziol Zh

View full text Add to dashboard Cite

The review summarizes generalizing modern scientific data on the main functions of the protein HMGB1, and its physiological and pathological roles. Amphoterin is involved in key processes that ensure the functioning of DNA in the cell nucleus and plays an important role outside it. HMGB1 has been implicated in many human inflammatory diseases such as sepsis, ischemic reperfusion injury, neurological conditions, cardiovascular disease, autoimmune disease, and others. This manuscript describes the structure and main functions of HMGB1, discusses the significance of this alarmin as damage-associated molecular patterns, and analyzes its role in the development of inflammation and cell death. Special attention is focused on the role of HMGB1 in the development of endotoxemia, as well as data on the signaling pathways involved in its pathogenesis. Information on the results of studies of the possibility of modulating the activity of this protein using inhibitors is also considered, since understanding this may be useful for developing new therapeutic strategies aimed at treating inflammatory conditions of various origins.

show abstract

Molecular insights into the multifaceted functions and therapeutic targeting of high mobility group box 1 in metabolic diseases

Cited by 11 publications

References 61 publications

Periplaneta americana extract alleviates steatohepatitis in a mouse model by modulating HMGB1-mediated inflammatory response

Periplaneta americana extract alleviates steatohepatitis in a mouse model by modulating HMGB1-mediated inflammatory response

The clinical significance of serum HMGB1 in patients with lower extremity arteriosclerosis obliterans after interventional vascular restenosis

Multifunctional Activity of Nuclear Protein Amphoterin and Its Role in Endotoxemia

Contact Info

Product

Resources

About