Pterostilbene ameliorates the disrupted Adars expression and improves liver fibrosis in DEN-induced liver injury in Wistar rats: A novel potential effect

Mohamad, Magda I.; Desoky, Islam A; Zaki, Kamelia Ahmed; Sadek, Doaa; Kassim, Samar K.; Mohamed, Dalia Abdel-Wahab

doi:10.1016/j.gene.2021.146124

Cited by 8 publications

(8 citation statements)

References 56 publications

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“…DEN is a nitrosamine-containing chemical reagent, and its toxic properties in mammals are well established [21][22][23]. Studies have shown that oral administration of the smallest quantities of DEN or dimethylnitrosamine (DMN) results in severe hepatic cell injury in both animals and humans [24][25][26][27].…”

Section: The Chemical Reagent (Den)-induced Liver Fibrosis/cirrhosis ...mentioning

confidence: 99%

“…As such, applied C57BL/6 wild-type inbred mice with a single diet of 0.014% DEN in drinking water; 6 days/week for 15 weeks, we successfully induced a liver fibrosis/cirrhosis/cancer mouse model [19]. The model shows that DEN is extremely effective in inducing hepatic fibrosis [21], cirrhosis and cancers (Figure 1B) that are compatible with the deterioration of liver functions [22,35].…”

Section: The Chemical Reagent (Den)-induced Liver Fibrosis/cirrhosis ...mentioning

confidence: 99%

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Survival Fate of Hepatic Stem/Progenitor and Immune Cells in a Liver Fibrosis/Cirrhosis Animal Model and Clinical Implications

Yan¹,

Hu²,

Wu³

et al. 2023

Animal Models and Experimental Research in Medicine

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This chapter provides novel information about the survival features of hepatic resident stem/progenitor cells (NG2+ HSPs) during liver fibrosis/cirrhotic development. A well-defined diethylnitrosamine (DEN)-induced liver fibrosis/cirrhotic/cancer mouse model was developed to evaluate the fate of the HSPs and its clinical implications. This model possess three time-zones during the disease development: fibrosis (3–5 weeks post-DEN), cirrhosis (6–10 weeks post-DEN), and cancers (up to 10 weeks post-DEN). During this process, the model represents histological patterns similar to those described in humans and shows better survival of the HSPs in the fibrotic zone, which was correlated with inflammatory signals, as compared to the cirrhotic zone. It has also been discovered that immune CD8+ T cells in the fibrotic zone are beneficial in liver fibrosis resolution, suggesting that the fibrotic time zone is important for mobilizing endogenous HSPs and cell-based therapy. As such, we hypothesize that clinical strategies in fibrotic/cirrhotic liver treatment are necessary either in time at the fibrotic phase or to adopt an approach of regulating HSP viability when the disease develops into the cirrhotic phase.

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Section: The Chemical Reagent (Den)-induced Liver Fibrosis/cirrhosis ...mentioning

confidence: 99%

Section: The Chemical Reagent (Den)-induced Liver Fibrosis/cirrhosis ...mentioning

confidence: 99%

Survival Fate of Hepatic Stem/Progenitor and Immune Cells in a Liver Fibrosis/Cirrhosis Animal Model and Clinical Implications

Yan¹,

Hu²,

Wu³

et al. 2023

Animal Models and Experimental Research in Medicine

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“… 18 Disruption in the expression of hepatic ADAR1 and ADAR2 could potentially lead to liver dysfunction, triggering liver inflammation and liver fibrosis. 19 …”

Section: Introductionmentioning

confidence: 99%

ADAR2 deficiency ameliorates non‐alcoholic fatty liver disease and muscle atrophy through modulating serum amyloid A1

Kung,

Yang,

Lin

et al. 2024

J cachexia sarcopenia muscle

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BackgroundNon‐alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease worldwide. Sarcopenia is a syndrome characterized by progressive and generalized loss of skeletal muscle mass and strength, which is commonly associated with NAFLD. Adenosine‐to‐inosine editing, catalysed by adenosine deaminase acting on RNA (ADAR), is an important post‐transcriptional modification of genome‐encoded RNA transcripts. Three ADAR gene family members, including ADAR1, ADAR2 and ADAR3, have been identified. However, the functional role of ADAR2 in obesity‐associated NAFLD and sarcopenia remains unclear.MethodsADAR2+/+/GluR‐BR/R mice (wild type [WT]) and ADAR2−/−/GluR‐BR/R mice (ADAR2 knockout [KO]) were subjected to feeding with standard chow or high‐fat diet (HFD) for 20 weeks at the age of 5 weeks. The metabolic parameters, hepatic lipid droplet, grip strength test, rotarod test, muscle weight, fibre cross‐sectional area (CSA), fibre types and protein associated with protein degradation were examined. Systemic and local tissues serum amyloid A1 (SAA1) were measured. The effects of SAA1 on C2C12 myotube atrophy were investigated.ResultsADAR2 KO mice fed with HFD exhibited lower body weight (−7.7%, P < 0.05), lower liver tissue weight (−20%, P < 0.05), reduced liver lipid droplets in concert with a decrease in hepatic triglyceride content (−24%, P < 0.001) and liver injury (P < 0.01). ADAR2 KO mice displayed protection against HFD‐induced glucose intolerance, insulin resistance and dyslipidaemia. Skeletal muscle mass (P < 0.01), muscle strength (P < 0.05), muscle endurance (P < 0.001) and fibre size (CSA; P < 0.0001) were improved in ADAR2 KO mice fed with HFD compared with WT mice fed with HFD. Muscle atrophy‐associated transcripts, such as forkhead box protein O1, muscle atrophy F‐box/atrogin‐1 and muscle RING finger 1/tripartite motif‐containing 63, were decreased in ADAR2 KO mice fed with HFD compared with WT mice fed with HFD. ADAR2 deficiency attenuates HFD‐induced local liver and skeletal muscle tissue inflammation. ADAR2 deficiency abolished HFD‐induced systemic (P < 0.01), hepatic (P < 0.0001) and muscular (P < 0.001) SAA1 levels. C2C12 myotubes treated with recombinant SAA1 displayed a decrease in myotube length (−37%, P < 0.001), diameter (−20%, P < 0.01), number (−39%, P < 0.001) and fusion index (−46%, P < 0.01). Myogenic markers (myosin heavy chain and myogenin) were decreased in SAA1‐treated myoblast C2C12 cells.ConclusionsThese results provide novel evidence that ADAR2 deficiency may be important in obesity‐associated sarcopenia and NAFLD. Increased SAA1 might be involved as a regulatory factor in developing sarcopenia in NAFLD.

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Section: Introductionmentioning

confidence: 99%

“…In eukaryotes, gene duplication events gave rise to several organelle-specific isoforms. Their subcellular localization of HSP70 changes depending on cellular conditions (Mattos et al 2022; Mohamad et al 2022; Velazquez and Lindquist 1984), but the organelle-specific isoforms can be clearly distinguished by taking advantage of phylogenetic analyses. Namely, metazoan HSP70s have been robustly classified into four lineages, cytosolic A (HSP70cA), cytosolic B (HSP70cB), endoplasmic reticulum (ER) (HSP70er), and mitochondria (HSP70m), in Bayesian and maximum likelihood frameworks (Schnebert et al 2022; Yu et al 2021), which has been supported by several genome-wide HSP70 screening studies (Grewal et al 2022; Hasnain and Kaneko; Kaneko 2022; Liu et al 2022).…”

Section: Introductionmentioning

confidence: 99%

Genomic loss of the HSP70cA gene in the vertebrate lineage

Merchant

Ramirez

Reyes

et al. 2022

Preprint

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Metazoan 70 kDa heat shock protein (HSP70) genes have been classified into four lineages: cytosolic A (HSP70cA), cytosolic B (HSP70cB), endoplasmic reticulum (HSP70er), and mitochondria (HSP70m). Because previous studies have identified no HSP70cA genes in vertebrates, we hypothesized that this gene has lost on the evolutionary path to vertebrates. To test this hypothesis, the present study conducted a comprehensive database search followed by phylogenetic and synteny analyses. The HSP70cA gene was present in invertebrates and animals that belong to subphyla of Chordata, Cephalochordata (lancelets) and Tunicata (tunicates). However, the genomes of early vertebrates in the subphylum Craniata (lamprey, hagfish, elephant shark, and coelacanth) contained only HSP70cB genes, suggesting the loss of the HSP70cA gene in the early period of vertebrate evolution. Synteny analysis using available genomic resources indicated that the synteny around the HSP70 genes was generally conserved between tunicates, but it was largely different between tunicates and lamprey. These results suggest the presence of dynamic chromosomal rearrangement in early vertebrates, which possibly caused the loss of the HSP70cA gene in the vertebrate lineage.

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Pterostilbene ameliorates the disrupted Adars expression and improves liver fibrosis in DEN-induced liver injury in Wistar rats: A novel potential effect

Cited by 8 publications

References 56 publications

Survival Fate of Hepatic Stem/Progenitor and Immune Cells in a Liver Fibrosis/Cirrhosis Animal Model and Clinical Implications

Survival Fate of Hepatic Stem/Progenitor and Immune Cells in a Liver Fibrosis/Cirrhosis Animal Model and Clinical Implications

ADAR2 deficiency ameliorates non‐alcoholic fatty liver disease and muscle atrophy through modulating serum amyloid A1

Genomic loss of the HSP70cA gene in the vertebrate lineage

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