&lt;p&gt;Gut Dysbiosis and Increased Intestinal Permeability Drive microRNAs, NLRP-3 Inflammasome and Liver Fibrosis in a Nutritional Model of Non-Alcoholic Steatohepatitis in Adult Male Sprague Dawley Rats&lt;/p&gt;

Longo, Larisse; Ferrari, Jéssica Tonin; Rampelotto, Pabulo Henrique; Dellavia, Gustavo Hirata; Pasqualotto, Amanda; Oliveira, C.P.; Cerski, Carlos Thadeu Schmidt; Silveira, Themis Reverbel da; Cruz, Carolina Uribe; Álvares‐da‐Silva, Mário Reis

doi:10.2147/ceg.s262879

Cited by 29 publications

(24 citation statements)

References 68 publications

(94 reference statements)

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“…In addition to exerting direct insulin-sensitizing, anti-inflammatory, and anti-fibrotic actions in the liver parenchyma, the vitamin D/VDR system participates also to the maintenance of systemic insulin sensitivity and to the homeostasis of organs involved in MAFLD pathogenesis, such as the gut and the adipose tissue [37][38][39][40][41].…”

Section: Vitamin D/vdr Axis In the Pathophysiology Of Mafldmentioning

confidence: 99%

“…Indeed, several studies demonstrated that vitamin D/VDR axis is involved in the modulation of gut microbiota [82][83][84][85][86][87][88][89][90][91], which in turn impacts on the development of MAFLD in obesity [41]. The genetic ablation of VDR in mice induces gut dysbiosis, reducing Lactobacillus and increasing Clostridium and Bacteroides concentrations [86].…”

Section: Vitamin D/vdr Axis In the Pathophysiology Of Mafldmentioning

confidence: 99%

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Vitamin D and Metabolic Dysfunction-Associated Fatty Liver Disease (MAFLD): An Update

2020

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Non-alcoholic fatty liver disease (NAFLD) is the first cause of chronic liver disease worldwide; it ranges from simple steatosis to steatohepatitis (NASH) and, potentially, cirrhosis and hepatocarcinoma. NAFLD is also an independent risk factor for type 2 diabetes, cardiovascular diseases, and mortality. As it is largely associated with insulin resistance and related disorders, NAFLD has been recently re-named as Metabolic dysfunction-Associated Fatty Liver Disease (MAFLD). At present, there are no approved pharmacological treatments for this condition. Vitamin D is a molecule with extensive anti-fibrotic, anti-inflammatory, and insulin-sensitizing properties, which have been proven also in hepatic cells and is involved in immune-metabolic pathways within the gut–adipose tissue–liver axis. Epidemiological data support a relationship hypovitaminosis D and the presence of NAFLD and steatohepatitis (NASH); however, results from vitamin D supplementation trials on liver outcomes are controversial. This narrative review provides an overview of the latest evidence on pathophysiological pathways connecting vitamin D to NAFLD, with emphasis on the effects of vitamin D treatment in MAFLD by a nonsystematic literature review of PubMed published clinical trials. This article conforms to the Scale for Assessment of Narrative Review Articles (SANRA) guidelines. Evidence so far available supports the hypothesis of potential benefits of vitamin D supplementation in selected populations of NAFLD patients, as those with shorter disease duration and mild to moderate liver damage.

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Section: Vitamin D/vdr Axis In the Pathophysiology Of Mafldmentioning

confidence: 99%

Section: Vitamin D/vdr Axis In the Pathophysiology Of Mafldmentioning

confidence: 99%

Vitamin D and Metabolic Dysfunction-Associated Fatty Liver Disease (MAFLD): An Update

2020

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“…In this study, our results further showed that GSDMD expression, an executor of pyroptosis, is significantly increased in gastric mucosa with H. pylori infection, which is in line with the result displayed that GSDMD is drastically decreased in gastric epithelial cells in response to rabeprazole stimulation, a regimen for H. pylori-infectious treatment. What's more, the inappropriate activation of the NLRP3 inflammasome could contribute to the onset and progression of various diseases [38], such as obesity [39], type 2 diabetes [40], inflammatory bowel disease [41], rheumatoid arthritis [42], liver fibrosis [43], Myocardial infarctions [44]. In addition to both NF-KB and SREBP-1c have been reported to regulate NLRPs transcription [17,18,20,45], the further work is required to address the mechanism through which rabeprazole regulated NLRP3, leading to inhibit NLRP3 inflammasome in future work.…”

Section: Discussionmentioning

confidence: 99%

Rabeprazole inhibits inflammatory reaction by inhibition of cell pyroptosis in gastric epithelial cells

Xie

Fan

Xiong

et al. 2021

BMC Pharmacol Toxicol

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Background Helicobacter pylori (H. pylori) is a common pathogen in development of peptic ulcers with pyroptosis. Rabeprazole, a critical component of standard triple therapy, has been widely used as the first-line regimen for H. pylori infectious treatment. The aim of this study to explore the function of Rabeprazole on cell pyroptosis in vitro. Methods The clinical sample from patients diagnosed with or without H. pylori-infection were collected to analyze by Immunohistochemistry (IHC). Real-time quantitative PCR (qPCR), western blot (WB) and enzyme linked immunosorbent assay (Elisa) were performed to analyze the effect of Rabeprazole on cell pyroptosis, including LDH, IL-1β and IL-18. Results In this study, we showed that Rabeprazole regulated a phenomenon of cell pyroptosis as confirmed by lactate dehydrogenase (LDH) assay. Further results showed that Rabeprazole inhibited cell pyroptosis in gastric epithelial cells by alleviating GSDMD-executed pyroptosis, leading to decrease IL-1β and IL-18 mature and secretion, which is attributed to NLRP3 inflammasome activation inhibition. Further analysis showed that ASC, NLRP3 and Caspase-1, was significantly repressed in response to Rabeprazole stimulation, resulting in decreasing cleaved-caspase-1 expression. Most important, NLRP3 and GSDMD is significantly increased in gastric tissue of patients with H. pylori infection. Conclusion These findings revealed a critical role of Rabeprazole in cell pyroptosis in patients with H. pylori infection, suggesting that targeting cell pyroptosis is an alternative strategy in improving H. pylori treatment.

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“…Modifications of miRNAs expression is connected with several chronic liver diseases, including NAFLD (103, 104), alcohol-related liver disease (105), cirrhosis, and HCC (106). Moreover, the impact of diet or gut-microbiota derived metabolites in the regulation of miRNAs expression in the gut and in the liver was demonstrated by multiple studies (106)(107)(108)(109).…”

Section: Micro-rna (Mirna)mentioning

confidence: 99%

Molecular and Cellular Mediators of the Gut-Liver Axis in the Progression of Liver Diseases

et al. 2021

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The gut-liver axis covers the bidirectional communication between the gut and the liver, and thus includes signals from liver-to-gut (e.g., bile acids, immunoglobulins) and from gut-to-liver (e.g., nutrients, microbiota-derived products, and recirculating bile acids). In a healthy individual, liver homeostasis is tightly controlled by the mostly tolerogenic liver resident macrophages, the Kupffer cells, capturing the gut-derived antigens from the blood circulation. However, disturbances of the gut-liver axis have been associated to the progression of varying chronic liver diseases, such as non-alcoholic fatty liver disease, non-alcoholic steatohepatitis, and primary sclerosing cholangitis. Notably, changes of the gut microbiome, or intestinal dysbiosis, combined with increased intestinal permeability, leads to the translocation of gut-derived bacteria or their metabolites into the portal vein. In the context of concomitant or subsequent liver inflammation, the liver is then infiltrated by responsive immune cells (e.g., monocytes, neutrophils, lymphoid, or dendritic cells), and microbiota-derived products may provoke or exacerbate innate immune responses, hence perpetuating liver inflammation and fibrosis, and potentiating the risks of developing cirrhosis. Similarly, food derived antigens, bile acids, danger-, and pathogen-associated molecular patterns are able to reshape the liver immune microenvironment. Immune cell intracellular signaling components, such as inflammasome activation, toll-like receptor or nucleotide-binding oligomerization domain-like receptors signaling, are potent targets of interest for the modulation of the immune response. This review describes the current understanding of the cellular landscape and molecular pathways involved in the gut-liver axis and implicated in chronic liver disease progression. We also provide an overview of innovative therapeutic approaches and current clinical trials aiming at targeting the gut-liver axis for the treatment of patients with chronic liver and/or intestinal diseases.

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<p>Gut Dysbiosis and Increased Intestinal Permeability Drive microRNAs, NLRP-3 Inflammasome and Liver Fibrosis in a Nutritional Model of Non-Alcoholic Steatohepatitis in Adult Male Sprague Dawley Rats</p>

Cited by 29 publications

References 68 publications

Vitamin D and Metabolic Dysfunction-Associated Fatty Liver Disease (MAFLD): An Update

Vitamin D and Metabolic Dysfunction-Associated Fatty Liver Disease (MAFLD): An Update

Rabeprazole inhibits inflammatory reaction by inhibition of cell pyroptosis in gastric epithelial cells

Molecular and Cellular Mediators of the Gut-Liver Axis in the Progression of Liver Diseases

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