Immune and Metabolic Alterations in Liver Fibrosis: A Disruption of Oxygen Homeostasis?

Li, Xinyu; Zhang, Quyan; Wang, Zeyu; Zhuang, Quan; Zhao, Mingyi

doi:10.3389/fmolb.2021.802251

Cited by 7 publications

(4 citation statements)

References 124 publications

(136 reference statements)

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“…Hypoxia-inducible factor (HIF) is an important factor that is activated when hypoxia occurs and considered to be an essential factor for cirrhosis. The effects of oxygen imbalance on metabolism and immunity of cirrhosis is a potential new target for anti-fibrotic therapyv [13].…”

Section: Discussionmentioning

confidence: 99%

The Effect of MSCs with/without Silymarin Against Liver Fibrosis in HepG2 Cell Line with Focused on Caspase3, NFKβ, Apoptosis, Proliferation, Necrosis, and Collagen

2023

IJCMER

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Background: Liver fibrosis is characterized by irreversible damage to the liver parenchyma. The mechanism of fibrosis is based on the activation of collagen, nuclear factor kappa (NF-kβ) activation, and inhibition of ne-crosis, apoptosis, caspase-3 and proliferation. The HepG2 cell line is an evolved human liver cancer cell that exhibits a human hormone response. Hepatocyte stem cells have antifibrotic, anti-inflammatory, and im-munomodulatory properties, can suppress apoptosis and necrosis, and promote proliferation. Methods: This is an experimental in vitro study using pre-test and post-test. Hepatocyte stem cells were obtained from the neonatal umbilical cord. The cell lines were divided into four groups. Analysis was performed on below variable including caspase-3, NF-kβ, necrosis, apoptosis, proliferation and cytopathological capacity. Results: Cytopathological studies of the hepG2 cell line showed fibroblast growth. Mesenchymal stem cells reduced NF-kβ activity, but not caspase 3 activity. Mesenchymal stem cells also significantly reduced apoptosis and necrotic activity, but silymarin was not significantly affected. Mesenchymal stem cells also significantly increased proliferation (p <0.001), but silymarin was not significantly affected. Conclusion: Mesenchymal stem cells significantly inhibited NF-kβ, necrosis, apoptosis, and proliferation ac-tivation, but caspase-3 inhibition was not significantly affected.

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Section: Discussionmentioning

confidence: 99%

The Effect of MSCs with/without Silymarin Against Liver Fibrosis in HepG2 Cell Line with Focused on Caspase3, NFKβ, Apoptosis, Proliferation, Necrosis, and Collagen

2023

IJCMER

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“…Recent studies in the NASH research field addressed the pathogenic role of low-grade inflammation and vascular impairment, perturbed immunometabolism, and a prothrombotic milieu, finally culminating in profibrogenic hepatic hypoxia [ 116 ]. In this context, Arelaki et al investigated neutrophil extracellular traps (NETs), acknowledged to be involved in the pathogenesis of various noninfectious proinflammatory and prothrombotic conditions, in liver biopsies of 20 individuals with NASH [ 117 ].…”

Section: Nash As a Metabolic Disorder: Epidemiology And Mechanismsmentioning

confidence: 99%

Endpoints in NASH Clinical Trials: Are We Blind in One Eye?

Lonardo,

Ballestri,

Mantovani

et al. 2024

Metabolites

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This narrative review aims to illustrate the notion that nonalcoholic steatohepatitis (NASH), recently renamed metabolic dysfunction-associated steatohepatitis (MASH), is a systemic metabolic disorder featuring both adverse hepatic and extrahepatic outcomes. In recent years, several NASH trials have failed to identify effective pharmacological treatments and, therefore, lifestyle changes are the cornerstone of therapy for NASH. with this context, we analyze the epidemiological burden of NASH and the possible pathogenetic factors involved. These include genetic factors, insulin resistance, lipotoxicity, immuno-thrombosis, oxidative stress, reprogramming of hepatic metabolism, and hypoxia, all of which eventually culminate in low-grade chronic inflammation and increased risk of fibrosis progression. The possible explanations underlying the failure of NASH trials are also accurately examined. We conclude that the high heterogeneity of NASH, resulting from variable genetic backgrounds, exposure, and responses to different metabolic stresses, susceptibility to hepatocyte lipotoxicity, and differences in repair-response, calls for personalized medicine approaches involving research on noninvasive biomarkers. Future NASH trials should aim at achieving a complete assessment of systemic determinants, modifiers, and correlates of NASH, thus adopting a more holistic and unbiased approach, notably including cardiovascular–kidney–metabolic outcomes, without restricting therapeutic perspectives to histological surrogates of liver-related outcomes alone.

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“…Most of the electrons migrate down through the ETC to cytochrome c oxidase and then combine with protons and O 2− to form water, but there are still electrons leaking from the ETC that directly react with oxygen to form mt-ROS, such as superoxide anion (O 2− ), H 2 O 2 , etc. In recent years, mitochondrial dysfunction and abnormal production of mitochondrial ROS have been widely detected in MAFLD and MASH [77][78][79][80][81][82]. In MAFLD, activation of MPTPs and mt-DNA mutations could reduce the activity of complexes on the ETC, which is the main reason for electron leakage.…”

Section: Oxidative Phosphorylationmentioning

confidence: 99%

Mitochondrial Dysfunction in Metabolic Dysfunction Fatty Liver Disease (MAFLD)

Zhao,

Zhou,

Wang

et al. 2023

IJMS

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Nonalcoholic fatty liver disease (NAFLD) has become an increasingly common disease in Western countries and has become the major cause of liver cirrhosis or hepatocellular carcinoma (HCC) in addition to viral hepatitis in recent decades. Furthermore, studies have shown that NAFLD is inextricably linked to the development of extrahepatic diseases. However, there is currently no effective treatment to cure NAFLD. In addition, in 2020, NAFLD was renamed metabolic dysfunction fatty liver disease (MAFLD) to show that its pathogenesis is closely related to metabolic disorders. Recent studies have reported that the development of MAFLD is inextricably associated with mitochondrial dysfunction in hepatocytes and hepatic stellate cells (HSCs). Simultaneously, mitochondrial stress caused by structural and functional disorders stimulates the occurrence and accumulation of fat and lipo-toxicity in hepatocytes and HSCs. In addition, the interaction between mitochondrial dysfunction and the liver–gut axis has also become a new point during the development of MAFLD. In this review, we summarize the effects of several potential treatment strategies for MAFLD, including antioxidants, reagents, and intestinal microorganisms and metabolites.

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Immune and Metabolic Alterations in Liver Fibrosis: A Disruption of Oxygen Homeostasis?

Cited by 7 publications

References 124 publications

The Effect of MSCs with/without Silymarin Against Liver Fibrosis in HepG2 Cell Line with Focused on Caspase3, NFKβ, Apoptosis, Proliferation, Necrosis, and Collagen

The Effect of MSCs with/without Silymarin Against Liver Fibrosis in HepG2 Cell Line with Focused on Caspase3, NFKβ, Apoptosis, Proliferation, Necrosis, and Collagen

Endpoints in NASH Clinical Trials: Are We Blind in One Eye?

Mitochondrial Dysfunction in Metabolic Dysfunction Fatty Liver Disease (MAFLD)

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