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

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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.

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Data availability

The original sequencing data are available at the NCBI SRA database: PRJNA706528.

References

  • Baffy G (2015) MicroRNAs in nonalcoholic fatty liver disease. J Clin Med 4:1977–1988

    Article  CAS  Google Scholar 

  • Bang C, Thum T (2012) Exosomes: new players in cell-cell communication. Int J Biochem Cell Biol 44:2060–2064

    Article  CAS  Google Scholar 

  • Berlanga A, Guiu-Jurado E, Porras JA, Auguet T (2014) Molecular pathways in non-alcoholic fatty liver disease. Clin Exp Gastroenterol 7:221–239

    PubMed  PubMed Central  Google Scholar 

  • Buzzetti E, Pinzani M, Tsochatzis EA (2016) The multiple-hit pathogenesis of non-alcoholic fatty liver disease (NAFLD). Metabolism 65:1038–1048

    Article  CAS  Google Scholar 

  • Chalasani N, Younossi Z, Lavine JE, Charlton M, Cusi K, Rinella M, Harrison SA, Brunt EM, Sanyal AJ (2018) The diagnosis and management of nonalcoholic fatty liver disease: practice guidance from the american association for the study of liver diseases. Hepatology 67:328–357

    Article  Google Scholar 

  • Christodoulides C, Lagathu C, Sethi JK, Vidal-Puig A (2009) Adipogenesis and WNT signaling. Trends Endocrinol Metab 20:16–24

    Article  CAS  Google Scholar 

  • Csak T, Bala S, Lippai D, Satishchandran A, Catalano D, Kodys K, Szabo G (2015) microRNA-122 regulates hypoxia-inducible factor-1 and vimentin in hepatocytes and correlates with fibrosis in diet-induced steatohepatitis. Liver Int 35:532–541

    Article  CAS  Google Scholar 

  • Esler WP, Bence KK (2019) Metabolic targets in nonalcoholic fatty liver disease. Cell Mol Gastroenterol Hepatol 8:247–267

    Article  Google Scholar 

  • Fang YL, Chen H, Wang CL, Liang L (2018) Pathogenesis of non-alcoholic fatty liver disease in children and adolescence: From “two hit theory” to “multiple hit model.” World J Gastroenterol 24:2974–2983

    Article  CAS  Google Scholar 

  • Ipsen DH, Lykkesfeldt J, Tveden-Nyborg P (2018) Molecular mechanisms of hepatic lipid accumulation in non-alcoholic fatty liver disease. Cell Mol Life Sci 75:3313–3327

    Article  CAS  Google Scholar 

  • Ismaiel A, Dumitrascu DL (2019) Cardiovascular risk in fatty liver disease: the liver-heart axis-literature review. Front Med (lausanne) 6:202

    Article  Google Scholar 

  • Kornek M, Lynch M, Mehta SH, Lai M, Exley M, Afdhal NH, Schuppan D (2012) Circulating microparticles as disease-specific biomarkers of severity of inflammation in patients with hepatitis C or nonalcoholic steatohepatitis. Gastroenterology 14:3448–3458

    Google Scholar 

  • Li S, Chen X, Zhang H, Liang X, Xiang Y, Yu C, Zen K, Li Y, Zhang CY (2009a) Differential expression of microRNAs in mouse liver under aberrant energy metabolic status. J Lipid Res 50:1756–1765

    Article  CAS  Google Scholar 

  • Li ZZ, Berk M, McIntyre TM, Feldstein AE (2009b) Hepatic lipid partitioning and liver damage in nonalcoholic fatty liver disease: role of stearoyl-CoA desaturase. J Biol Chem 28456:37–44

    Google Scholar 

  • Li S, Hong M, Tan HY, Wang N, Feng Y (2016) Insights into the role and interdependence of oxidative stress and inflammation in liver diseases. Oxid Med Cell Longev 2016:4234061

    PubMed  PubMed Central  Google Scholar 

  • Lin Q, Gao Z, Alarcon RM, Ye J, Yun Z (2009) A role of miR-27 in the regulation of adipogenesis. FEBS J 27623:48–58

    Google Scholar 

  • Liu XL, Cao HX, Fan JG (2016) MicroRNAs as biomarkers and regulators of nonalcoholic fatty liver disease. J Dig Dis 17:708–715

    Article  CAS  Google Scholar 

  • Masarone M, Rosato V, Dallio M, Gravina AG, Aglitti A, Loguercio C, Federico A, Persico M (2018) role of oxidative stress in pathophysiology of nonalcoholic fatty liver disease. Oxid Med Cell Longev 2018:9547613

    Article  Google Scholar 

  • Momen-Heravi F, Bala S, Kodys K, Szabo G (2015) Exosomes derived from alcohol-treated hepatocytes horizontally transfer liver specific miRNA-122 and sensitize monocytes to LPS. Sci Rep 2015:59991

    Google Scholar 

  • Nakanishi N, Nakagawa Y, Tokushige N, Aoki N, Matsuzaka T, Ishii K, Yahagi N, Kobayashi K, Yatoh S, Takahashi A et al (2009) The up-regulation of microRNA-335 is associated with lipid metabolism in liver and white adipose tissue of genetically obese mice. Biochem Biophys Res Commun 385(4):92–96

    Article  Google Scholar 

  • Otsuka M, Kishikawa T, Yoshikawa T, Yamagami M, Ohno M, Takata A, Shibata C, Ishibashi R, Koike K (2017) MicroRNAs and Liver disease. J Hum Genet 62:75–80

    Article  CAS  Google Scholar 

  • Pappachan JM, Babu S, Krishnan B, Ravindran NC (2017) Non-alcoholic fatty liver disease: a clinical update. J Clin Transl Hepatol 5:384–393

    PubMed  PubMed Central  Google Scholar 

  • Salvoza NC, Klinzing DC, Gopez-Cervantes J, Baclig MO (2016) Association of circulating serum miR-34a and miR-122 with dyslipidemia among patients with non-alcoholic fatty liver disease. PLoS ONE 11:e0153497

    Article  Google Scholar 

  • Thomou T, Mori MA, Dreyfuss JM, Konishi M, Sakaguchi M, Wolfrum C, Rao TN, Winnay JN, Garcia-Martin R, Grinspoon SK et al (2017) Adipose-derived circulating miRNAs regulate gene expression in other tissues. Nature 542:450–455

    Article  CAS  Google Scholar 

  • Videla LA, Pettinelli P (2012) Misregulation of PPAR functioning and its pathogenic consequences associated with nonalcoholic fatty liver disease in human obesity. PPAR Res 2012:107434

    Article  Google Scholar 

  • Vos MB, Abrams SH, Barlow SE, Caprio S, Daniels SR, Kohli R, Mouzaki M, Sathya P, Schwimmer JB, Sundaram SS et al (2017) 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). J Pediatr Gastroenterol Nutr 64:319–334

    Article  Google Scholar 

  • Wang T, Li M, Guan J, Li P, Wang H, Guo Y, Shuai S, Li X (2011) MicroRNAs miR-27a and miR-143 regulate porcine adipocyte lipid metabolism. Int J Mol Sci 127:950–959

    Google Scholar 

  • Wang H, Hou L, Li A, Duan Y, Gao H, Song X (2014) Expression of serum exosomal microRNA-21 in human hepatocellular carcinoma. Biomed Res Int 2014:864894

    PubMed  PubMed Central  Google Scholar 

  • Xing LJ, Zhang L, Liu T, Hua YQ, Zheng PY, Ji G (2011) Berberine reducing insulin resistance by up-regulating IRS-2 mRNA expression in nonalcoholic fatty liver disease (NAFLD) rat liver. Eur J Pharmacol 6684:67–71

    Google Scholar 

  • Xiong WJ, Hu LJ, Jian YC, Wang LJ, Jiang M, Li W, He Y (2012) Wnt5a participates in hepatic stellate cell activation observed by gene expression profile and functional assays. World J Gastroenterol 1817:45–52

    Google Scholar 

  • Ying W, Riopel M, Bandyopadhyay G, Dong Y, Birmingham A, Seo JB, Ofrecio JM, Wollam J, Hernandez-Carretero A, Fu W et al (2017) Adipose tissue macrophage-derived exosomal miRNAs can modulate In Vivo? and In Vitro? insulin sensitivity. Cell 171:372-384e12

    Article  CAS  Google Scholar 

  • Zhang S, Ouyang X, Jiang X, Gu D, Lin Y, Kong SK, Xie W (2015) Dysregulated serum MicroRNA expression profile and potential biomarkers in hepatitis C virus-infected patients. Int J Med Sci 125:90–98

    Google Scholar 

  • Zhang F, Li SP, Zhang T, Yu B, Zhang J, Ding HG, Ye FJ, Yuan H, Ma YY, Pan HT et al (2021) High throughput microRNAs sequencing profile of serum exosomes in women with and without polycystic ovarian syndrome. PeerJ 9:e10998

    Article  Google Scholar 

  • Zhou XL, Fu JF (2018) Expert consensus on the diagnosis and treatment of non-alcoholic fatty liver disease in children. Chin J Pract Pediatrics 7:487–492

    Google Scholar 

Download references

Funding

This work was supported by the National Natural Science Foundation of China (82071729), Health Commission of Zhejiang Province, China (2021KY1155, 2018KY843, 2018KY847).

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Authors and Affiliations

  1. Shaoxing Maternity and Child Health Care Hospital, Shaoxing, 312000, China

    Jian-Wei Zhang & Hai-Tao Pan

  2. Obstetrics and Gynecology Hospital of Shaoxing University, Shaoxing, China

    Jian-Wei Zhang & Hai-Tao Pan

Authors
  1. Jian-Wei Zhang
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  2. Hai-Tao Pan
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Correspondence to Hai-Tao Pan.

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Conflict of interest

Jian-Wei Zhang and Hai-Tao Pan declare that they have no conflict of interest.

Ethical approval

This study had been approved by the Ethics Committee of Shaoxing Maternal and Child Health Care Hospital. Informed consent was obtained from all individual participants included in the study.

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Zhang, JW., Pan, HT. microRNA profiles of serum exosomes derived from children with nonalcoholic fatty liver. Genes Genom 44, 879–888 (2022). https://doi.org/10.1007/s13258-021-01150-8

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  • DOI: https://doi.org/10.1007/s13258-021-01150-8

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