MicroRNAs as biomarkers and regulators of nonalcoholic fatty liver disease

Liu, Xiao Lin; Cao, Hai Xia; Fan, Jian Gao

doi:10.1111/1751-2980.12408

Cited by 26 publications

(21 citation statements)

References 80 publications

(178 reference statements)

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“…(7) It has been reported that miRs regulate lipid metabolism, inflammation, and fibrosis in NAFLD through the posttranscriptional silencing of the target genes by base-pairing to partially complementary sites in the 3′-untranslated region (UTR) of target mRNA. (8) The miR-192-5p is one of the most abundant miRNAs in liver tissue. (9) Research suggests that serum miR-192-5p levels can be used as a potential biomarker for disease progression of NAFLD.…”

Section: Approach and Resultsmentioning

confidence: 99%

Lipotoxic Hepatocyte‐Derived Exosomal MicroRNA 192‐5p Activates Macrophages Through Rictor/Akt/Forkhead Box Transcription Factor O1 Signaling in Nonalcoholic Fatty Liver Disease

et al. 2020

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Background and Aims Hepatic macrophages can be activated by many factors such as gut‐derived bacterial components and factors released from damaged hepatocytes. Macrophage polarization toward a proinflammatory phenotype (M1) represents an important event in the disease progression of nonalcoholic fatty liver disease (NAFLD). However, the underlying molecular mechanisms remain incompletely understood. Exosomes have been identified as important mediators for cell–cell communication by transferring various biological components such as microRNAs (miRs), proteins, and lipids. The role of exosomes in crosstalk between hepatocytes and macrophages in disease progression of NAFLD is yet to be explored. Approach and Results In the present study, we reported that lipotoxic injury–induced release of hepatocyte exosomes enriched with miR‐192‐5p played a critical role in the activation of M1 macrophages and hepatic inflammation. Serum miR‐192‐5p levels in patients with NAFLD positively correlated with hepatic inflammatory activity score and disease progression. Similarly, the serum miR‐192‐5p level and the number of M1 macrophages, as well as the expression levels of the hepatic proinflammatory mediators, were correlated with disease progression in high‐fat high‐cholesterol diet–fed rat models. Lipotoxic hepatocytes released more miR‐192‐5p‐enriched exosomes than controls, which induced M1 macrophage (cluster of differentiation 11b–positive [CD11b+]/CD86+) activation and increase of inducible nitric oxide synthase, interleukin 6, and tumor necrosis factor alpha expression. Furthermore, hepatocyte‐derived exosomal miR‐192‐5p inhibited the protein expression of the rapamycin‐insensitive companion of mammalian target of rapamycin (Rictor), which further inhibited the phosphorylation levels of Akt and forkhead box transcription factor O1 (FoxO1) and resulted in activation of FoxO1 and subsequent induction of the inflammatory response. Conclusions Hepatocyte‐derived exosomal miR‐192‐5p plays a critical role in the activation of proinflammatory macrophages and disease progression of NAFLD through modulating Rictor/Akt/FoxO1 signaling. Serum exosomal miR‐192‐5p represents a potential noninvasive biomarker and therapeutic target for nonalcoholic steatohepatitis.

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Section: Approach and Resultsmentioning

confidence: 99%

Lipotoxic Hepatocyte‐Derived Exosomal MicroRNA 192‐5p Activates Macrophages Through Rictor/Akt/Forkhead Box Transcription Factor O1 Signaling in Nonalcoholic Fatty Liver Disease

et al. 2020

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“…Similarly, a recent study reported that miRNA-34a had moderate accuracy for distinguishing between NASH and NAFL (AUROC=0.78) [44]. Our study involved a total of 14 miRNAs, which have several roles in the pathogenesis of NAFLD [14,45], such as, lipid synthesis (miRNA-122), fatty acid b-oxidation (miRNA-34a, -122), endoplasmic reticulum stress (miRNA-30, -34a, -122), in ammation (miRNA-34a, -99a, -146b), brosis (miRNA-122), tumorigenesis (miRNA-99a), and cell autophagy and apoptosis (miRNA-34a). The relationships between miRNAs and NASH pathogenesis can be both one-to-many and many-to-one.…”

Section: Discussionmentioning

confidence: 71%

“…In brief, miRNAs can suppress or promote expression of target genes [41]. miRNAs widely participate in multiple pathological processes of NAFLD [14,41], and their serum levels differ signi cantly between healthy individuals and NAFLD patients. Hence, they have become a new potential non-invasive biomarker for diagnosis of NAFLD.…”

Section: Discussionmentioning

confidence: 99%

“…Many experiments and clinical trials have con rmed that miRNAs are closely related to NAFLD [10][11][12][13]. miRNAs target a variety of genes related to lipid metabolism and pro-in ammatory factors, that are involved in pathogenesis of NAFLD [14]. A recent meta-analysis reported that circulating miRNA has moderate diagnostic accuracy in NAFLD [15].…”

Section: Introductionmentioning

confidence: 99%

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Efficacy of serum miRNA test as a non-invasive method to diagnose nonalcoholic steatohepatitis: a systematic review and meta-analysis.

Xin

Zhan

Chen

et al. 2020

Preprint

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1. Background: Nonalcoholic steatohepatitis (NASH) is a key turning point during the progression of nonalcoholic fatty liver disease (NAFLD). Recent studies have shown that serum miRNA tests may be effective in the diagnosis of NAFLD. We conducted a meta-analysis to assess the evidence for the diagnostic efficacy of serum miRNAs in patients with NAFLD and its subtype, NASH, in particular. 2. Methods: After a systematic review, sensitivity, specificity, and area under the receiver operating characteristics curve (AUROC) were pooled to determine the efficacy of serum miRNA test for the diagnosis of NAFLD and NASH. Clinical utility was evaluated by Fagan’s nomogram and likelihood ratio scattergram. Heterogeneity was evaluated by subgroup analysis and meta-regression. Publication bias was detected by Deeks’ funnel plot. 3. Results: We included 27 trials containing 1775 NAFLD patients (including simple steatosis and NASH) and 586 NASH patients. For NAFLD vs NASH, the pooled sensitivity, specificity, and AUROC were (0.71 vs. 0.74), (0.76 vs. 0.85) and (0.80 vs. 0.86), respectively. Serum miRNA had high accuracy for distinguishing NASH from simple steatosis, with an AUROC of 0.91. Among the most commonly studied serum miRNAs , miRNA-34a showed moderate diagnostic accuracy for NAFLD and the lowest heterogeneity (sensitivity I 2 = 5.73%, specificity I 2 = 33.16%, AUROC = 0.85). According to subgroup analysis and meta-regression, a lower BMI ( < 30 kg/m 2 ) might be a crucial source of heterogeneity. 4.Conclusions: As a novel non-invasive method, serum miRNA test exhibited robust diagnostic efficacy for NASH. Among these well-studied miRNAs, miRNA-34a was more available for diagnosis. Diagnosis of NAFLD by serum miRNA is more likely to be accurate in patients with BMI ≥ 30kg/m 2 .

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“…MicroRNAs are small, non‐coding RNAs which regulate the expression of numerous target genes at both transcriptional and translational levels. Altered microRNA profiles have been found in liver injury in both human and experimental animal models . MicroRNA‐122 (miR‐122), the most abundant microRNA in the liver, constitutes about 70% of all microRNAs in mature hepatocytes, and decreased levels of hepatic miR‐122 has been found from patients as well as animals with ALD/NASH .…”

Section: Introductionmentioning

confidence: 99%

Protective effect of isochlorogenic acid B on liver fibrosis in non‐alcoholic steatohepatitis of mice

Liu

Huang

Niu

et al. 2018

Basic Clin Pharma Tox

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Liver fibrosis is a common symptom of non-alcoholic steatohepatitis (NASH) and a worldwide clinical issue. The miR-122/HIF-1α signalling pathway is believed to play an important role in the genesis of progressive fibrosis. Isochlorogenic acid B (ICAB), naturally isolated from Laggera alata, is verified to have antioxidative and hepatoprotective properties. The aim of this study was to investigate the effect of ICAB on liver fibrosis in NASH and its potential protective mechanisms. NASH was induced in a mouse model with a methionine- and choline-deficient (MCD) diet for 4 weeks, and ICAB was orally administered every day at three doses (5, 10 and 20 mg/kg). Pathological results indicated that ICAB significantly improved the pathological lesions of liver fibrosis. The levels of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and hepatic hydroxyproline (Hyp), cholesterol (CHO) and triglyceride (TG) were also significantly decreased by ICAB. In addition, ICAB inhibited hepatic stellate cells (HSCs) activation and the expressions of hepatic genes involved in liver fibrosis including LOX, TGF-β1, MCP-1, COL1α1 and TIMP-1. ICAB also attenuated liver oxidative stress through Nrf2 signalling pathway. What is more, the decreased levels of miR-122 and over-expression of hepatic HIF-1α could be reversed by ICAB treatment. These results simultaneously confirmed that ICAB had a significant protective effect on fibrosis in NASH by inhibiting oxidative stress via Nrf2 and suppressing multiple profibrogenic factors through miR-122/HIF-1α signalling pathway.

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MicroRNAs as biomarkers and regulators of nonalcoholic fatty liver disease

Cited by 26 publications

References 80 publications

Lipotoxic Hepatocyte‐Derived Exosomal MicroRNA 192‐5p Activates Macrophages Through Rictor/Akt/Forkhead Box Transcription Factor O1 Signaling in Nonalcoholic Fatty Liver Disease

Lipotoxic Hepatocyte‐Derived Exosomal MicroRNA 192‐5p Activates Macrophages Through Rictor/Akt/Forkhead Box Transcription Factor O1 Signaling in Nonalcoholic Fatty Liver Disease

Efficacy of serum miRNA test as a non-invasive method to diagnose nonalcoholic steatohepatitis: a systematic review and meta-analysis.

Protective effect of isochlorogenic acid B on liver fibrosis in non‐alcoholic steatohepatitis of mice

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