Is serum high-mobility group box 1 (HMGB-1) level correlated with liver fibrosis in chronic hepatitis B?

İnkaya, Ahmet Çağkan; Demir, Nazlım Aktuğ; Kölgelier, Servet; Sümer, Şua; Demir, Lütfi Saltuk; Ural, Onur; Pehlivan, Fatma Seher; Aslan, Mine; Arpacı, Abdullah

doi:10.1097/md.0000000000007547

Cited by 16 publications

(18 citation statements)

References 22 publications

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“…High-mobility group box-1 (HMGB-1) is a ubiquitous protein, identified as an alarmin molecule, participating in the pathogenesis of acute as well as chronic liver injuries. 1,17 HMGB-1 protein contains two similar DNAbinding domains A-box and B-box, each with three α helices that fold into an L-or V-shaped structure containing a negatively charged acidic tail that interacts with specific residues within and between the HMG boxes and thus regulates the 3D structure and DNA binding of the protein. 18 Hepatocytes actively secrete HMGB-1 in response to oxidative stress induced by pro-oxidants, and appear to be the major cellular source of HMGB-1 in the damaged liver.…”

Section: Introductionmentioning

confidence: 99%

Suppression of Cisplatin-Induced Hepatic Injury in Rats Through Alarmin High-Mobility Group Box-1 Pathway by Ganoderma lucidum: Theoretical and Experimental Study

Hassan

Al-Wahaibi

Elmorsy

et al. 2020

DDDT

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Purpose: Drug-induced liver injury (DILI) is the most common cause of acute liver failure. The aim of this study was to investigate the molecular mechanisms by which Ganoderma lucidum mushroom (GLM) may ameliorate cisplatin (CP)-induced hepatotoxicity theoretically and experimentally. Materials and Methods: Thirty-six male Sprague-Dawley (SD) rats were divided into six groups, two of them are normal and Ganoderma lucidum control groups. Liver injury was induced by a single dose of CP (12 mg/kg i.p) in four groups, one of them is CP control group. Besides cisplatin injection in day 1, rats in groups (4-6) were subjected to GLM (500 mg/kg/day) either every other day or daily oral dose or via i.p injection for 10 consecutive days. Results: In this study, GLM supplementation caused significant reduction of elevated highmobility group box-1 (HMGB-1) with a concurrent decline in TNF-α and upregulation of IL-10 compared to the CP group (P<0.05). The histopathological and fibrosis evaluation significantly confirmed the improvement upon simultaneous treatment with GLM. Moreover, immunohistochemical examination also confirmed the recovery following GLM treatment indicated by downregulation of NF-κB, p53 and caspase-3 along with upsurge of B-cell lymphoma 2 (Bcl-2) expression (P<0.05). GLM treatment significantly decreased serum levels of hepatic injury markers; ALT, AST, T. bilirubin as well as oxidative stress markers; MDA and H 2 O 2 with a concomitant increase in hepatic GSH and SOD. Also, the performed docking simulation of ganoderic acid exhibited good fitting and binding with HMGB-1 through hydrogen bond formation with conservative amino acids which gives a strong evidence for its hepatoprotective effect and may interpret the effect of Ganoderma lucidum. Conclusion: GLM attenuated hepatic injury through downregulation of HMGB-1/NF-kB and caspase-3 resulted in modulation of the induced oxidative stress and the subsequent cross-talk between the inflammatory and apoptotic cascade indicating its promising role in DILI.

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Section: Introductionmentioning

confidence: 99%

Suppression of Cisplatin-Induced Hepatic Injury in Rats Through Alarmin High-Mobility Group Box-1 Pathway by Ganoderma lucidum: Theoretical and Experimental Study

Hassan

Al-Wahaibi

Elmorsy

et al. 2020

DDDT

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“…HMGB1 was originally discovered as a nuclear protein; however, when it is passively released or actively secreted after injury or cell stimulation, HMGB1 meets all the criteria of a damage-associated molecular pattern (DAMP) and works as a necrosis signal for the immune system through cell-surface receptors. (12)(13)(14) In this latter role, HMGB1 acts as a proinflammatory cytokine that contributes to multiple injuries, including those from the liver, such as warm and cold ischemia/reperfusion (I/R) injury, (15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27) sepsis, (23,(28)(29)(30)(31)(32) acetaminophen (APAP) intoxication, (23,(33)(34)(35)(36)(37)(38)(39)(40) alcoholic liver disease (ALD), (41)(42)(43) fibrosis, (44)(45)(46)(47)(48)(49) nonalcoholic steatohepatitis (NASH), (50)(51)(52) and hepatocellular carcinoma (HCC). (53)…”

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confidence: 99%

“…HMGB1 was originally discovered as a nuclear protein; however, when it is passively released or actively secreted after injury or cell stimulation, HMGB1 meets all the criteria of a damage‐associated molecular pattern (DAMP) and works as a necrosis signal for the immune system through cell‐surface receptors . In this latter role, HMGB1 acts as a proinflammatory cytokine that contributes to multiple injuries, including those from the liver, such as warm and cold ischemia/reperfusion (I/R) injury, sepsis, acetaminophen (APAP) intoxication, alcoholic liver disease (ALD), fibrosis, nonalcoholic steatohepatitis (NASH), and hepatocellular carcinoma (HCC) . By binding cell‐surface receptors on immune cells, HMGB1 activates intracellular signaling pathways that regulate immune cell function, including chemotaxis and cytokine production .…”

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confidence: 99%

High‐Mobility Group Box‐1 and Liver Disease

Gaskell

Nieto

2018

Hepatology Communications

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High‐mobility group box‐1 (HMGB1) is a ubiquitous protein. While initially thought to be simply an architectural protein due to its DNA‐binding ability, evidence from the last decade suggests that HMGB1 is a key protein participating in the pathogenesis of acute liver injury and chronic liver disease. When it is passively released or actively secreted after injury, HMGB1 acts as a damage‐associated molecular pattern that communicates injury and inflammation to neighboring cells by the receptor for advanced glycation end products or toll‐like receptor 4, among others. In the setting of acute liver injury, HMGB1 participates in ischemia/reperfusion, sepsis, and drug‐induced liver injury. In the context of chronic liver disease, it has been implicated in alcoholic liver disease, liver fibrosis, nonalcoholic steatohepatitis, and hepatocellular carcinoma. Recently, specific posttranslational modifications have been identified that could condition the effects of the protein in the liver. Here, we provide a detailed review of how HMGB1 signaling participates in acute liver injury and chronic liver disease.

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“…chronic liver failure, hepatic cancer cirrhosis, and several of these conditions can cause hepatic I/R injury (Inkaya et al, 2017;Li et al, 2016;Zheng et al, 2015). Thus, HMGB1 may be a therapeutic target for the treatment of hepatic I/R injury.…”

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confidence: 99%

MicroRNA‐449b‐5p targets HMGB1 to attenuate hepatocyte injury in liver ischemia and reperfusion

Zhang

et al. 2019

Journal Cellular Physiology

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MicroRNAs (miRNAs) participate in the pathological process of liver ischemia/reperfusion (I/R) injury. MiR‐449b‐5p is the target miRNA of high mobility group box 1 (HMGB1). Its role and molecular mechanism in liver I/R injury remain unidentified. In this study, we found a protective effect of miR‐449b‐5p against hepatic I/R injury. HMGB1 expression significantly increased, whereas miR‐449b‐5p dramatically decreased in patients after liver transplant and in L02 cells exposed to hypoxia/reoxygenation (H/R). A dual‐luciferase reporter assay confirmed the direct interaction between miR‐449b‐5p and the 3′ untranslated region of HMGB1 messenger RNA. We also found that overexpression of miR‐449b‐5p significantly promoted cell viability and inhibited cell apoptosis of L02 cells exposed to H/R. Moreover, miR‐449b‐5p repressed HMGB1 protein expression and nuclear factor‐κB (NF‐κB) pathway activation in these L02 cells. In an in vivo rat model of hepatic I/R injury, overexpression of miR‐449b‐5p significantly decreased alanine aminotransferase and aspartate aminotransferase and inhibited the HMGB1/NF‐κB pathway. Our study thus suggests that miR‐449b‐5p alleviated hepatic I/R injury by targeting HMGB1 and deactivating the NF‐κB pathway, which may provide a novel and promising therapeutic target for hepatic I/R injury.

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Is serum high-mobility group box 1 (HMGB-1) level correlated with liver fibrosis in chronic hepatitis B?

Abstract: In this study, we demonstrated that serum HMGB1 levels increase in the early course of liver injury and this increase is not correlated with severity of the liver damage.

Cited by 16 publications

References 22 publications

<p>Suppression of Cisplatin-Induced Hepatic Injury in Rats Through Alarmin High-Mobility Group Box-1 Pathway by <em>Ganoderma lucidum</em>: Theoretical and Experimental Study</p>

<p>Suppression of Cisplatin-Induced Hepatic Injury in Rats Through Alarmin High-Mobility Group Box-1 Pathway by <em>Ganoderma lucidum</em>: Theoretical and Experimental Study</p>

High‐Mobility Group Box‐1 and Liver Disease

MicroRNA‐449b‐5p targets HMGB1 to attenuate hepatocyte injury in liver ischemia and reperfusion

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