Endoplasmic reticulum stress and liver diseases

Li, Xiaoying; Green, Richard M.

doi:10.1016/j.livres.2019.01.002

Cited by 124 publications

(97 citation statements)

References 156 publications

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“…The accumulation of HBV transcripts may induce a stress response as the stress-related genes INHBE, FAM129A, SESN2, ASNS, and CHAC1 were all upregulated ( Fig 7; see also the functional annotation results in Supplementary Table S7). Indeed, previous studies have also shown that HBV infection could lead to endoplasmic reticulum stress (46)(47)(48) , including upregulation of INHBE (49) . Interestingly, 3 significantly upregulated genes (ADM2, AKNA, and SH3BP2) were previously shown to correlate with the Ishak fibrosis stage (50) .…”

Section: Hbv Replication Had Little Effect On the Host Gene Expressionmentioning

confidence: 98%

Quantitative analysis of the splice variants expressed by the major hepatitis B virus genotypes

Lim

Sozzi

Revill

et al. 2020

Preprint

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Hepatitis B virus (HBV) is a major human pathogen that causes liver diseases. The main HBV RNAs are unspliced transcripts that encode the key viral proteins. Recent studies show that some of the HBV spliced transcript isoforms are predictive of liver cancer, yet the roles of these spliced transcripts remain elusive. Furthermore, a total of 9 major HBV genotypes were isolated from discrete geographical regions of the world, it is likely that these genotypes may express a broad variety of spliced transcript isoforms. To systematically study the HBV splice variants, we transfected the human hepatoma cells Huh7 with 4 HBV genotypes (A2, B2, C2, and D3), followed by deep RNA-sequencing. We found that 12-25% of HBV RNAs were splice variants, which were reproducibly detected across independent biological replicates. This accounted for a total of 6 novel and 6 previously identified splice variants. In particular, two highly abundant novel splice variants, in which we called the putative splice variants 1 and 5 (pSP1 and pSP5), were specifically expressed at high levels in genotypes D3 and B2, respectively. In general, the HBV splicing profiles varied across the genotypes except for the known spliced pgRNAs SP1 and SP9, which were present in all 4 major genotypes. Counterintuitively, these singly spliced SP1 and SP9 had a suboptimal 5′ splice site, suggesting that splicing of HBV RNAs is tightly controlled by the viral post-transcriptional regulatory RNA element.

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Section: Hbv Replication Had Little Effect On the Host Gene Expressionmentioning

confidence: 98%

Quantitative analysis of the splice variants expressed by the major hepatitis B virus genotypes

Lim

Sozzi

Revill

et al. 2020

Preprint

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“…Several studies have shown that ER stress contributes to the development of ALD. 48 To investigate the comorbidity of ALD and metabolic syndrome, we have recently applied the mouse model of chronic-binge EtOH liver injury (NIAAA model) to obese KK-A y mice. 49 Chronic-plusbinge EtOH intake induced massive hepatic steatosis along with hepatocyte apoptosis and inflammation, and increased ER stress markers including binding immunoglobulin protein (BiP), unspliced and spliced forms of X-box-binding protein-1 (uXBP1 and sXBP1, respectively), inositol trisphosphate receptor (IP3R), and C/EBP homologous protein (CHOP), and also enhanced the oxidative stress markers heme oxygenase-1 and 4-hydroxynonenal.…”

Section: Cellular Stress Responses In Nafld and Aldmentioning

confidence: 99%

Nonalcoholic fatty liver disease and alcohol-related liver disease: From clinical aspects to pathophysiological insights

2020

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Two major causes of steatohepatitis are alcohol and metabolic syndrome. Although the underlying causes of alcoholrelated liver disease (ALD) and nonalcoholic fatty liver disease (NAFLD)/nonalcoholic steatohepatitis (NASH) differ, there are certain similarities in terms of the mode of disease progression and underlying pathophysiological mechanisms. Further, excessive alcohol consumption is often seen in patients with metabolic syndrome, and alcoholic hepatitis exacerbation by comorbidity with metabolic syndrome is an emerging clinical problem. There are certain ethnic differences in the development of both NAFLD and ALD. Especially, Asian populations tend to be more susceptible to NAFLD, and genetic polymorphisms in patatin-like phospholipase domain-containing 3 (PNPLA3) play a key role in both NAFLD and ALD. From the viewpoint of pathophysiology, cellular stress responses, including autophagy and endoplasmic reticulum (ER) stress, are involved in the development of cellular injury in steatohepatitis. Further, gutderived bacterial products and innate immune responses in the liver most likely play a profound role in the pathogenesis of both ALD and NASH. Though the recent progress in the treatment of viral hepatitis has reduced the prevalence of viral-related development of hepatocellular carcinoma (HCC), non-viral HCC is increasing. Alcohol and metabolic syndrome synergistically exacerbate progression of steatohepatitis, resulting in carcinogenesis. The gut-liver axis is a potential therapeutic and prophylactic target for steatohepatitis and subsequent carcinogenesis.

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“…These ROS products impair the activity of deiodinases [ 148 ], enhance lipid peroxidation, activation of the KCs, and of specific pro-inflammatory cytokines. Among them, the TNF-α and transforming growth factor β (TGF-β) activate hepatic satellite cells and endorse fibrosis [ 149 , 150 ]. THs modulate the hepatocyte mitochondrial function by the uncoupling of oxidative phosphorylation [ 151 ], and generate ROS through Ca 2+ –calcium/calmodulin-dependent protein kinase kinase 2 (CAMKK2)–5′-AMP-activated protein kinase (AMPK) circuit.…”

Section: Immunopathogenesismentioning

confidence: 99%

Hypothyroidism-Induced Nonalcoholic Fatty Liver Disease (HIN): Mechanisms and Emerging Therapeutic Options

Gosav

Neculae

Costea

et al. 2020

IJMS

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Nonalcoholic fatty liver disease (NAFLD) is an emerging worldwide problem and its association with other metabolic pathologies has been one of the main research topics in the last decade. The aim of this review article is to provide an up-to-date correlation between hypothyroidism and NAFLD. We followed evidence regarding epidemiological impact, immunopathogenesis, thyroid hormone-liver axis, lipid and cholesterol metabolism, insulin resistance, oxidative stress, and inflammation. After evaluating the influence of thyroid hormone imbalance on liver structure and function, the latest studies have focused on developing new therapeutic strategies. Thyroid hormones (THs) along with their metabolites and thyroid hormone receptor β (THR-β) agonist are the main therapeutic targets. Other liver specific analogs and alternative treatments have been tested in the last few years as potential NAFLD therapy. Finally, we concluded that further research is necessary as well as the need for an extensive evaluation of thyroid function in NAFLD/NASH patients, aiming for better management and outcome.

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Endoplasmic reticulum stress and liver diseases

Cited by 124 publications

References 156 publications

Quantitative analysis of the splice variants expressed by the major hepatitis B virus genotypes

Quantitative analysis of the splice variants expressed by the major hepatitis B virus genotypes

Nonalcoholic fatty liver disease and alcohol-related liver disease: From clinical aspects to pathophysiological insights

Hypothyroidism-Induced Nonalcoholic Fatty Liver Disease (HIN): Mechanisms and Emerging Therapeutic Options

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