miR-125b promotes the NF-κB-mediated inflammatory response in NAFLD via directly targeting TNFAIP3

Zhang, Qian; Yu, Kun; Cao, Yazhen; Luo, Yanli; Liu, Yan; Zhao, Caiyan

doi:10.1016/j.lfs.2021.119071

Cited by 32 publications

(20 citation statements)

References 28 publications

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“…( 32 ) miR‐125b promotes the NF‐κB‐mediated inflammatory response in hepatocytes from NAFLD. ( 33 ) We have previously demonstrated that SCT/SCTR‐mediated down‐regulation of miR‐125b promotes biliary proliferation and liver fibrosis during cholestasis, ( 6,21 ) whereas overexpression of miR‐125b protects HFD‐induced hepatic steatosis. ( 16 ) In our study, miR‐125b expression was decreased in human NAFLD/NASH liver and WT HFD mouse cholangiocytes, which was reversed by Sct or Sctr knockout.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of Secretin/Secretin Receptor Axis Ameliorates NAFLD Phenotypes

Chen

Kennedy

et al. 2021

Hepatology

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Background and Aims Human NAFLD is characterized at early stages by hepatic steatosis, which may progress to NASH when the liver displays microvesicular steatosis, lobular inflammation, and pericellular fibrosis. The secretin (SCT)/secretin receptor (SCTR) axis promotes biliary senescence and liver fibrosis in cholestatic models through down‐regulation of miR‐125b signaling. We aim to evaluate the effect of disrupting biliary SCT/SCTR/miR‐125b signaling on hepatic steatosis, biliary senescence, and liver fibrosis in NAFLD/NASH. Approach and Results In vivo, 4‐week‐old male wild‐type, Sct−/− and Sctr−/− mice were fed a control diet or high‐fat diet (HFD) for 16 weeks. The expression of SCT/SCTR/miR‐125b axis was measured in human NAFLD/NASH liver samples and HFD mouse livers by immunohistochemistry and quantitative PCR. Biliary/hepatocyte senescence, ductular reaction, and liver angiogenesis were evaluated in mouse liver and human NAFLD/NASH liver samples. miR‐125b target lipogenesis genes in hepatocytes were screened and validated by custom RT2 Profiler PCR array and luciferase assay. Biliary SCT/SCTR expression was increased in human NAFLD/NASH samples and in livers of HFD mice, whereas the expression of miR‐125b was decreased. Biliary/hepatocyte senescence, ductular reaction, and liver angiogenesis were observed in human NAFLD/NASH samples as well as HFD mice, which were decreased in Sct−/− and Sctr−/− HFD mice. Elovl1 is a lipogenesis gene targeted by miR‐125b, and its expression was also decreased in HFD mouse hepatocytes following Sct or Sctr knockout. Bile acid profile in fecal samples have the greatest changes between wild‐type mice and Sct−/−/Sctr−/− mice. Conclusion The biliary SCT/SCTR/miR‐125b axis promotes liver steatosis by up‐regulating lipid biosynthesis gene Elovl1. Targeting the biliary SCT/SCTR/miR‐125b axis may be key for ameliorating phenotypes of human NAFLD/NASH.

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Section: Discussionmentioning

confidence: 99%

Inhibition of Secretin/Secretin Receptor Axis Ameliorates NAFLD Phenotypes

Chen

Kennedy

et al. 2021

Hepatology

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“…Hence, a new disease named metabolic dysfunction-associated fatty liver disease (MAFLD) has been proposed to replace the old term NAFLD [ 11 , 12 ], and the new term MAFLD is used throughout this study. Enhanced hepatic lipid accumulation, oxidative stress and abnormal inflammatory response remain the foremost pillars in defining the pathogenesis of MAFLD [ 13 , 14 ]. Many studies have linked increased hepatic markers of oxidative stress and a reduction in antioxidant enzymes’ activity with the pathogenesis of MAFLD and NASH [ 15 , 16 ].…”

Section: Introductionmentioning

confidence: 99%

Hepatoprotective Effect of Bee Bread in Metabolic Dysfunction-Associated Fatty Liver Disease (MAFLD) Rats: Impact on Oxidative Stress and Inflammation

et al. 2021

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Metabolic dysfunction-associated fatty liver disease (MAFLD) is a pathological accumulation of hepatic lipid closely linked with many metabolic disorders, oxidative stress and inflammation. We aimed to evaluate the hepatoprotective effect of bee bread on oxidative stress and inflammatory parameters in MAFLD rats. Twenty-eight male Sprague-Dawley rats were assigned into four groups (n = 7/group): normal control (NC), high-fat diet (HFD), bee bread (HFD + Bb, HFD + 0.5 g/kg/day bee bread) and orlistat (HFD + Or, HFD + 10 mg/kg/day orlistat) groups. After 12 weeks, the HFD group demonstrated significantly higher body weight gain, serum levels of lipids (TG, TC, LDL), liver enzymes (AST, ALT, ALP) and adiponectin, liver lipids (TG, TC) and insulin resistance (HOMA-IR). Furthermore, the HFD group showed significantly decreased antioxidant enzyme activities (GPx, GST, GR, SOD, CAT) and GSH level, and increased liver oxidative stress (TBARS, NO), translocation of Nrf2 to the nucleus, Keap1 expression and inflammation (TNF-α, NF-κβ, MCP-1) together with histopathological alterations (steatosis, hepatocyte hypertrophy, inflammatory cell infiltration, collagen deposition), which indicated the presence of non-alcoholic steatohepatitis (NASH) and fibrosis. Bee bread significantly attenuated all these changes exerted by HFD feeding. In conclusion, our results suggest that bee bread might have antioxidant, anti-inflammatory, anti-steatotic and anti-fibrotic effects that are beneficial in protecting liver progression towards NASH and fibrosis.

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“…Tumor necrosis factor alpha-induced protein 3(TNFAIP3) is also known as A20, which is an endogenous negative regulator of NF-κB signaling, has been widely studied in several autoimmune and in ammatory disorders [27]. A recent study showed that TNFAIP3 was directly targeted by MiR-125b promoted the NF-κB-mediated in ammatory response in Non-alcoholic fatty liver disease(NAFLD) [28]. Deletions of the TNFAIP3 gene in innate immune cells of mice would develop autoin ammatory disease, which revealed the negative regulation of TNFAIP3 to innate immune cells [29].…”

Section: Discussionmentioning

confidence: 99%

Six Hub Genes Associated with Erectile Dysfunction And Acute Myocardial Infarction Based On GEO

Ang

Wang

et al. 2021

Preprint

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Background: Erectile dysfunction(ED) is a common male sexual dysfunction that significantly affects quality of life in men and induce a significant public health problem. Nowadays, vascular dysfunction is known as a common cause of ED. Acute myocardial infarction (AMI) became co-morbidity with ED as vascular event. The increasing number of males with both diseases is a public health problem that deserves our attention.Results: Seven commom genes of DEGs were obtained in ED and AMI. Fifteen terms mainly including I−kappaB kinase/NF−kappaB signaling et al and five KEGG pathways mainly including Toll−like receptor signaling pathway were also obtained. Further, the diagnostic value of top 6 hub genes were identified. Conclusion: The hub genes IKBKG, RIPK1, TNF, RPS27A, TLR2, and TNFAIP3 were selected and their diagnostic values were validated. They may play an important potential role in the occurrence and offer viable targets for treating inflammation-mediated vascular dysfunction in the ED and AMI.

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miR-125b promotes the NF-κB-mediated inflammatory response in NAFLD via directly targeting TNFAIP3

Cited by 32 publications

References 28 publications

Inhibition of Secretin/Secretin Receptor Axis Ameliorates NAFLD Phenotypes

Inhibition of Secretin/Secretin Receptor Axis Ameliorates NAFLD Phenotypes

Hepatoprotective Effect of Bee Bread in Metabolic Dysfunction-Associated Fatty Liver Disease (MAFLD) Rats: Impact on Oxidative Stress and Inflammation

Six Hub Genes Associated with Erectile Dysfunction And Acute Myocardial Infarction Based On GEO

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