MicroRNA-21 is associated with fibrosis in a rat model of nonalcoholic steatohepatitis and serves as a plasma biomarker for fibrotic liver disease

Takeuchi-Yorimoto, Ayano; Yamaura, Yu; Kanki, Masayuki; T, Ide; Nakata, Ayumi; Noto, Takahisa; Matsumoto, Masahiro

doi:10.1016/j.toxlet.2016.06.012

Cited by 25 publications

(18 citation statements)

References 28 publications

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“…Notably, we detected significant up-regulation of liver miR-21, miR-34a and miR-505 in NASH mice compared to lean mice (data was not shown). Since these microRNAs have been implicated in hepatic lipid homeostasis, inflammation, stellate cell activation and carcinogenesis [ 9 , 37 , 40 , 41 ]; our results strongly support that the circulating level of microRNA could reflect the status of the liver, and hence could be employed as non-invasive diagnostic tools for NASH.…”

Section: Discussionsupporting

confidence: 73%

“…MiR-192 regulates lipid synthesis in hepatocytes, and it was independently validated as biomarker for NASH by several groups using in vitro assays, animal models and clinical samples [ 12 , 13 , 34 – 36 ]. MiR-21 as biomarkers for hepatic fibrosis has been validated in both animal models and clinical samples [ 13 , 37 ]. Studies have also shown that miR-21 regulates the peroxisome proliferator-activated receptor α (PPARα) activity and associates with stellate cell activation [ 31 , 38 ].…”

Section: Discussionmentioning

confidence: 99%

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A circulating microRNA signature as noninvasive diagnostic and prognostic biomarkers for nonalcoholic steatohepatitis

Liu

Xiao

et al. 2018

BMC Genomics

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BackgroundNoninvasive biomarkers are urgently needed for patients with nonalcoholic steatohepatitis (NASH) to assist in diagnosis, monitoring disease progression and assessing treatment response. Recently several exploratory studies showed that circulating level of microRNA is associated with NASH and correlated with disease severity. Although these data were encouraging, the application of circulating microRNA as biomarkers for patient screening and stratification need to be further assessed under well-controlled conditions.ResultsThe expression of circulating microRNAs were profiled in diet-induced NASH progression and regression models to assess the diagnostic and prognostic values and the translatability between preclinical mouse model and men. Since these mice had same genetic background and were housed in the same conditions, there were minimal confounding factors. Histopathological lesions were analyzed at distinct disease progression stages along with microRNA measurement which allows longitudinal assessment of microRNA as NASH biomarkers. Next, differentially expressed microRNAs were identified and validated in an independent cohorts of animals. Thirdly, these microRNAs were examined in a NASH regression model to assess whether they would respond to NASH treatment.MicroRNA profiling in two independent cohorts of animals validated the up-regulation of 6 microRNAs (miR-122, miR-192, miR-21, miR-29a, miR-34a and miR-505) in NASH mice, which was designated as the circulating microRNA signature for NASH. The microRNA signature could accurately distinguish NASH mice from lean mice, and it responded to chow diet treatment in a NASH regression model. To further improve the performance of microRNA-based biomarker, a new composite biomarker was proposed, which consists of miR-192, miR-21, miR-505 and ALT. The new composite biomarker outperformed the microRNA signature in predicting NASH mice which had NAS > 3, and deserves further validations in large scale studies.ConclusionThe present study supported the translation of circulating microRNAs between preclinical models and humans in NASH pathogenesis and progression. The microRNA-based composite biomarker may be used for non-invasive diagnosis, clinical monitoring and assessing treatment response for NASH.Electronic supplementary materialThe online version of this article (10.1186/s12864-018-4575-3) contains supplementary material, which is available to authorized users.

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Section: Discussionsupporting

confidence: 73%

Section: Discussionmentioning

confidence: 99%

A circulating microRNA signature as noninvasive diagnostic and prognostic biomarkers for nonalcoholic steatohepatitis

Liu

Xiao

et al. 2018

BMC Genomics

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“…Thus, miRNAs is very likely to be the link between gut microbiota and NAFLD. The miRNAs we scanned were stably expressed in the liver and involved in the course of NAFLD such as hepatic steatosis (miR10b [ 60 ], miR-24 [ 61 ], miR-29a [ 62 ], miR-155 [ 63 ], miR-34a [ 64 ], miR-125b [ 65 ], miR-486 [ 66 ], miR-199a [ 67 ], miR-30b [ 68 ], miR-30c [ 69 ], miR467b [ 70 ], miR-148a [ 71 ]), insulin resistance (miR-125b [ 72 ], miR-206 [ 73 ], miR-130a [ 74 ], miR-291b [ 75 ]), inflammatory and hepatic fibrosis (miR-21a [ 76 , 77 ], miR-199a [ 78 ], miR-370 [ 79 ], miR-130a [ 80 ], miR-34a [ 81 ], miR-24 [ 82 ]), as well as cirrhosis and HCC (miR-210 [ 83 ], miR-10b [ 84 ]). We further analyzed the correlation between the alteration of gut microbiota and miRNAs.…”

Section: Discussionmentioning

confidence: 99%

Amelioration of hepatic steatosis is associated with modulation of gut microbiota and suppression of hepatic miR-34a in Gynostemma pentaphylla (Thunb.) Makino treated mice

Jia

Lin

et al. 2018

Nutr Metab (Lond)

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BackgroundNon-alcoholic fatty liver disease (NAFLD) is a chronic and progressive liver disease with an increased risk of morbidity and mortality. However, so far no specific pharmacotherapy has been approved. Gynostemma pentaphylla (Thunb.) Makino (GP) is a traditional Chinese medicine that is widely used against hyperlipemia as well as hyperglycemia. This study aims to evaluate the effect of GP on NAFLD and explore the possible mechanism.MethodsHigh-fat-diet induced NAFLD mice model were orally administrated with GP at dose of 11.7 g/kg or equivalent volume of distilled water once a day for 16 weeks. Body weight, food intake and energy expenditure were assessed to evaluate the general condition of mice. The triglycerides, total cholesterol content in the liver and liver histopathology, serum lipid profile and serum insulin level, fecal microbiome, hepatic microRNAs and relative target genes were analyzed.ResultsMice in GP treatment group displayed improved hepatic triglycerides content with lower lipid droplet in hepatocyte and NAFLD activity score. Besides, GP treatment altered the composition of gut microbiota and the relative abundance of some of the key components that are implicated in metabolic disorders, especially phylum Firmicutes (Eubacterium, Blautia, Clostridium and Lactobacillus). Several hepatic microRNAs were downregulated by GP treatment such as miR-130a, miR-34a, miR-29a, miR-199a, among which the expression miR-34a was altered by more than four-fold compared to that of HFD group (3:14). The correlation analysis showed that miR-34a was strongly related to the change of gut microbiota especially phylum Firmicutes (R = 0.796). Additionally, the target genes of miR-34a (HNF4α, PPARα and PPARα) were restored by GP both in mRNA and protein levels.ConclusionOur results suggested that GP modulated the gut microbiota and suppressed hepatic miR-34a, which was associated with the amelioration of hepatic steatosis.

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“…Hsa-miR-21-5p is associated with tumors in several organs [ 25 ] and several liver diseases including nonalcoholic steatohepatitis [ 26 ], drug-induced liver injury [ 27 ], and hepatocellular carcinoma [ 28 , 29 ]. However, the relationship between hsa-miR-21-5p and autoimmune disease has not been elucidated yet.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-223 and microRNA-21 in peripheral blood B cells associated with progression of primary biliary cholangitis patients

et al. 2017

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Recently, there is ample evidence suggesting the important role of microRNAs (miRNAs) in autoimmune diseases via modulating B cells function. Primary biliary cholangitis (PBC) is a progressive immune-mediated liver disease with unclear pathogenic mechanism. Whether the miRNA in peripheral B cells of PBC involve the mechanisms of pathology and progression is not known. The present study explores miRNA deregulation in peripheral B-cell of PBC from stage I to IV and healthy controls. Peripheral B cells were obtained from 72 PBC patients (stage I, n = 17; stage II, n = 23; stage III, n = 16; stage IV, n = 16) and 15 healthy controls. Initially, in a discovery study, miRNA array analysis was performed, subsequently, in a validation study, quantitative PCR was used to investigate miRNA expression profile in B cells of PBS patients compared to healthy controls. Based on bioinformatics analysis, we identified the potential biological processes and significant signaling pathways affected by these microRNAs, and generated the microRNA–gene network. The discovery study identified 558 miRNAs differentially expressed in B cells of PBC patients compared to controls. Interestingly, among all differentially expressed miRNAs, hsa-miR-223-3p and hsa-miR-21-5p were the only miRNAs that showed consistent and significant down-regulation from stage I to stage III of PBC. Bioinformatics showed that potential target genes of both miRNAs involved in migration, cell differentiation, apoptosis, and signal transduction pathways. In conclusion, our results suggest that the expression profiles of miRNA in peripheral B cells of PBC patients are closely associated with the disease progression, especially the down-regulation of hsa-miR-223-3p and hsa-miR-21-5p. Taken together, our study offers novel perspectives on the role of miRNAs in PBC pathogenesis.

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MicroRNA-21 is associated with fibrosis in a rat model of nonalcoholic steatohepatitis and serves as a plasma biomarker for fibrotic liver disease

Cited by 25 publications

References 28 publications

A circulating microRNA signature as noninvasive diagnostic and prognostic biomarkers for nonalcoholic steatohepatitis

A circulating microRNA signature as noninvasive diagnostic and prognostic biomarkers for nonalcoholic steatohepatitis

Amelioration of hepatic steatosis is associated with modulation of gut microbiota and suppression of hepatic miR-34a in Gynostemma pentaphylla (Thunb.) Makino treated mice

MicroRNA-223 and microRNA-21 in peripheral blood B cells associated with progression of primary biliary cholangitis patients

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