microRNA profiles of serum exosomes derived from children with nonalcoholic fatty liver

다국어 초록 (Multilingual Abstract)

Background: Nonalcoholic fatty liver disease (NAFLD) is a chronic disease caused by excessive fat accumulation in the liver in addition to alcohol consumption and other pathological factors. The incidence of NAFLD is rapidly growing, currently affecting 25% of the world population. Exosomes are extracellular vesicles containing a variety of biological molecules, including microRNAs (miRNAs).
Objective: To monitor the expression of exosomal microRNAs in the NAFLD.
Methods: In this study, five nonalcoholic fatty liver patients were included in the disease group, and five simple obesity patients were included in the control group. Exosomes from NAFLD patient serum were collected, and exosomal miRNAs were extracted. Exosomes were isolated and then confirmed by electron microscopy, nanoparticle tracking analysis (NTA) and western blotting. High-throughput sequencing methods were used to determine the expression profile of exosome-derived miRNAs.
Results: The sequencing results revealed that a total of 2588 miRNAs were identified. The expression of 80 miRNAs significantly differed between the NAFLD and control groups, including 30 upregulated and 50 downregulated miRNAs. miR-122-5p, miR-27a, and miR-335-5p may play an important role in NAFLD. Finally, GO and KEGG analyses were applied to explore the function of miRNA targets.
Conclusions: Collectively, this study identified some key exosomal miRNAs and pathways in NAFLD that might be used as molecular targets or diagnostic biomarkers for NAFLD.

참고문헌 (Reference)

1 Masarone M, "role of oxidative stress in pathophysiology of nonalcoholic fatty liver disease" 2018 : 9547613-, 2018

2 Csak T, "microRNA-122 regulates hypoxia-inducible factor-1 and vimentin in hepatocytes and correlates with fibrosis in diet-induced steatohepatitis" 35 : 532-541, 2015

3 Xiong WJ, "Wnt5a participates in hepatic stellate cell activation observed by gene expression profile and functional assays" 1817 : 45-52, 2012

4 Nakanishi N, "The up-regulation of microRNA-335 is associated with lipid metabolism in liver and white adipose tissue of genetically obese mice" 385 (385): 92-96, 2009

5 Buzzetti E, "The multiple-hit pathogenesis of non-alcoholic fatty liver disease(NAFLD)" 65 : 1038-1048, 2016

6 Chalasani N, "The diagnosis and management of nonalcoholic fatty liver disease : practice guidance from the american association for the study of liver diseases" 67 : 328-357, 2018

7 Fang YL, "Pathogenesis of nonalcoholic fatty liver disease in children and adolescence: From “two hit theory” to “multiple hit model.”" 24 : 2974-2983, 2018

8 Pappachan JM, "Non-alcoholic fatty liver disease : a clinical update" 5 : 384-393, 2017

9 Vos MB, "NASPGHAN Clinical Practice Guideline for the Diagnosis and Treatment of Nonalcoholic Fatty Liver Disease in Children : Recommendations from the Expert Committee on NAFLD(ECON)and the North American Society of Pediatric Gastroenterology, Hepatology and Nutrition(NASPGHAN)" 64 : 319-334, 2017

10 Berlanga A, "Molecular pathways in non-alcoholic fatty liver disease" 7 : 221-239, 2014

11 Ipsen DH, "Molecular mechanisms of hepatic lipid accumulation in non-alcoholic fatty liver disease" 75 : 3313-3327, 2018

12 Videla LA, "Misregulation of PPAR functioning and its pathogenic consequences associated with nonalcoholic fatty liver disease in human obesity" 2012 : 107434-, 2012

13 Wang T, "MicroRNAs miR-27a and miR-143 regulate porcine adipocyte lipid metabolism" 127 : 950-959, 2011

14 Baffy G, "MicroRNAs in nonalcoholic fatty liver disease" 4 : 1977-1988, 2015

15 Liu XL, "MicroRNAs as biomarkers and regulators of nonalcoholic fatty liver disease" 17 : 708-715, 2016

16 Otsuka M, "MicroRNAs and Liver disease" 62 : 75-80, 2017

17 Esler WP, "Metabolic targets in nonalcoholic fatty liver disease" 8 : 247-267, 2019

18 Li S, "Insights into the role and interdependence of oxidative stress and inflammation in liver diseases" 2016 : 4234061-, 2016

19 Zhang F, "High throughput microRNAs sequencing profile of serum exosomes in women with and without polycystic ovarian syndrome" 9 : e10998-, 2021

20 Li ZZ, "Hepatic lipid partitioning and liver damage in nonalcoholic fatty liver disease : role of stearoyl-CoA desaturase" 28456 : 37-44, 2009

21 Wang H, "Expression of serum exosomal microRNA-21 in human hepatocellular carcinoma" 2014 : 864894-, 2014

22 Zhou XL, "Expert consensus on the diagnosis and treatment of non-alcoholic fatty liver disease in children" 7 : 487-492, 2018

23 Momen-Heravi F, "Exosomes derived from alcohol-treated hepatocytes horizontally transfer liver specific miRNA-122 and sensitize monocytes to LPS" 2015 : 59991-, 2015

24 Bang C, "Exosomes : new players in cell-cell communication" 44 : 2060-2064, 2012

25 Zhang S, "Dysregulated serum MicroRNA expression profile and potential biomarkers in hepatitis C virus-infected patients" 125 : 90-98, 2015

26 Li S, "Differential expression of microRNAs in mouse liver under aberrant energy metabolic status" 50 : 1756-1765, 2009

27 Kornek M, "Circulating microparticles as disease-specific biomarkers of severity of inflammation in patients with hepatitis C or nonalcoholic steatohepatitis" 14 : 3448-3458, 2012

28 Ismaiel A, "Cardiovascular risk in fatty liver disease : the liver-heart axis-literature review" 6 : 202-, 2019

29 Xing LJ, "Berberine reducing insulin resistance by up-regulating IRS-2 mRNA expression in nonalcoholic fatty liver disease(NAFLD)rat liver" 6684 : 67-71, 2011

30 Salvoza NC, "Association of circulating serum miR-34a and miR-122 with dyslipidemia among patients with non-alcoholic fatty liver disease" 11 : e0153497-, 2016

31 Thomou T, "Adipose-derived circulating miRNAs regulate gene expression in other tissues" 542 : 450-455, 2017

32 Ying W, "Adipose tissue macrophage-derived exosomal miRNAs can modulate In Vivo? and In Vitro? insulin sensitivity" 171 : 372-384, 2017

33 Christodoulides C, "Adipogenesis and WNT signaling" 20 : 16-24, 2009

34 Lin Q, "A role of miR-27 in the regulation of adipogenesis" 27623 : 48-58, 2009