Journal of Korean Biological Nursing Science

Korean society of Biological Nursing Science (한국기초간호학회)
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Exosomal Protein Profiles as Novel Biomarkers in Weight Gain After Kidney Transplantation: A Pilot Study

  • Cho, Young-Eun (National Institute of Nursing Research, National Institutes of Health) ;
  • Lee, Hyangkyu (College of Nursing, Yonsei University) ;
  • Kim, Hyungsuk (National Institute of Nursing Research, National Institutes of Health) ;
  • Yun, Sijung (Yotta Biomed, LLC.) ;
  • Cashion, Ann (National Institute of Nursing Research, National Institutes of Health)
  • Received : 2020.03.23
  • Accepted : 2020.05.16
  • Published : 2020.05.31
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Abstract

Purpose:Weight gain after kidney transplantation is a critical factor that can lead to poor outcomes with cardiovascular complications. Many studies have been conducted to identify predictive markers of future weight changes at the time of transplant. Recently, circulating exosomes and its contents including miRNAs and proteins have attracted attention as potential biomarkers. In this pilot study, we investigated exosomal proteins and weight change after kidney transplant. Methods: Recipients (n = 10) were classified into two groups; weight gainers (n = 5, 9.7 ± 4.4kg) and weight losers (n = 5, -6.4 ± 1.8kg) based on their weight changes at 12-months posttransplant. Based on the exosomal protein profiles obtained by the LC-MS/MS, differentially expressed proteins were identified between the groups. Results: Concentration and the mean size of exosomes significantly increased at 12-months compared to the baseline (p= .009) in the total group. Eleven exosomal proteins were found at the baseline as differentially expressed between the two groups. In the weight gain group, complement proteins including HV169, C3, C4B, and C4A, were significantly upregulated. Conclusion: Our pilot study suggests that exosomal complementary proteins are associated with weight gain after kidney transplantation. Further studies are needed to clarify the role of these exosomal proteins in the underlying mechanisms of weight changes in kidney transplant recipients.

Keywords

References

  1. Lamb KE, Lodhi S, Meier-Kriesche HU. Long-term renal allograft survival in the United States: a critical reappraisal. American Journal of Transplantation. 2011;11(3):450-462. http://doi:10.1111/j.1600-6143.2010.03283.x.
  2. Aksoy N. Weight Gain After Kidney Transplant. Experimental and Clinical Transplant. 2016;14(Suppl 3):138-140.
  3. Vlassov AV, Magdaleno S, Setterquist R, Conrad R. Exosomes: current knowledge of their composition, biological functions, and diagnostic and therapeutic potentials. Biochimica et Biophysica Acta. 2012;1820(7):940-948. http://doi:10.1016/j.bbagen.2012.03.017.
  4. Takahashi A, Okada R, Nagao K, Kawamata Y, Hanyu A, Yoshimoto S, et al. Exosomes maintain cellular homeostasis by excreting harmful DNA from cells. Nature Communications. 2017;8:15287. http://doi:10.1038/ncomms15287.
  5. Tkach M, Thery C. Communication by extracellular vesicles: where we are and where we need to go. Cell. 2016;164(6):1226-1232. http://doi:10.1016/j.cell.2016.01.043.
  6. Bang C, Thum T. Exosomes: new players in cell-cell communication. The International Journal of Biochemistry & Cell Biology. 2012;44(11):2060-2064. http://doi:10.1016/j.biocel.2012.08.007.
  7. Huang-Doran I, Zhang CY, Vidal-Puig A. Extracellular vesicles: novel mediators of cell communication in metabolic disease. Trends in Endocrinology & Metabolism. 2017;28(1):3-18. http://doi:10.1016/j.tem.2016.10.003.
  8. Kranendonk ME, de Kleijn DP, Kalkhoven E, Kanhai DA, Uiterwaal CS, van der Graaf Y, et al. Extracellular vesicle markers in relation to obesity and metabolic complications in patients with manifest cardiovascular disease. Cardiovascular Diabetology. 2014;13:37. http://doi:10.1186/1475-2840-13-37.
  9. Gao X, Salomon C, Freeman DJ. Extracellular vesicles from adipose tissue-a potential role in obesity and type 2 diabetes? Frontiers in endocrinology (Lausanne). 2017;8:202. http://doi:10.3389/fendo.2017.00202.
  10. Stepanian A, Bourguignat L, Hennou S, Coupaye M, Hajage D, Salomon L, et al. Microparticle increase in severe obesity: not related to metabolic syndrome and unchanged after massive weight loss. Obesity (Silver Spring). 2013;21(11):2236-2243. http://doi:10.1002/oby.20365.
  11. Ferrante SC, Nadler EP, Pillai DK, Hubal MJ, Wang Z, Wang JM, et al. Adipocyte-derived exosomal miRNAs: a novel mechanism for obesity-related disease. Pediatric Research. 2015;77(3):447-454. http://doi:10.1038/pr.2014.202.
  12. Thomou T, Mori MA, Dreyfuss JM, Konishi M, Sakaguchi M, Wolfrum C, et al. Adipose-derived circulating miRNAs regulate gene expression in other tissues. Nature. 2017;542(7642):450-455. http://doi:10.1038/nature21365.
  13. Cashion A, Stanfill A, Thomas F, Xu L, Sutter T, Eason J, et al. Expression levels of obesity-related genes are associated with weight change in kidney transplant recipients. PLoS One. 2013;8(3):e59962. http://doi:10.1371/journal.pone.0059962.
  14. Cashion AK, Hathaway DK, Stanfill A, Thomas F, Ziebarth JD, Cui Y, et al. Pre-transplant predictors of one yr weight gain after kidney transplantation. Clinical Transplantation. 2014;28(11):1271-1278. http://doi:10.1111/ctr.12456.
  15. Mustapic M, Eitan E, Werner JK, Jr., Berkowitz ST, Lazaropoulos MP, Tran J, et al. Plasma extracellular vesicles enriched for neuronal origin: a potential window into brain pathologic processes. Frontiers in Neuroscience. 2017;11:278. http://doi:10.3389/fnins.2017.00278.
  16. Farrar CA, Kupiec-Weglinski JW, Sacks SH. The innate immune system and transplantation. Cold Spring Harbor Perspectives in Medicine. 2013;3(10):a015479. http://doi:10.1101/cshperspect.a015479.
  17. Sigdel TK, Ng YW, Lee S, Nicora CD, Qian W-J, Smith RD, et al. Perturbations in the urinary exosome in transplant rejection. Frontiers in Medicine. 2015;1(57):1-10. http://doi:10.3389/fmed.2014.00057.
  18. Dunkelberger JR, Song WC. Complement and its role in innate and adaptive immune responses. Cell Research. 2010;20(1):34-50. http://doi:10.1038/cr.2009.139.
  19. Puchau B, Zulet MA, Gonzalez de Echavarri A, Navarro-Blasco I, Martinez JA. Selenium intake reduces serum C3, an early marker of metabolic syndrome manifestations, in healthy young adults. European Journal of Clinical Nutrition. 2009;63(7):858-864. http://doi:10.1038/ejcn.2008.48.
  20. Liu Z, Tang Q, Wen J, Tang Y, Huang D, Huang Y, et al. Elevated serum complement factors 3 and 4 are strong inflammatory markers of the metabolic syndrome development: a longitudinal cohort study. Scientific Reports. 2016;6:18713. http://doi:10.1038/srep18713.
  21. Xin Y, Hertle E, van der Kallen CJH, Schalkwijk CG, Stehouwer CDA, van Greevenbroek MMJ. Complement C3 and C4, but not their regulators or activated products, are associated with incident metabolic syndrome: the CODAM study. Endocrine. 2018;62(3):617-627. http://doi:10.1007/s12020-018-1712-3.
  22. Dalli J, Norling LV, Renshaw D, Cooper D, Leung KY, Perretti M. Annexin 1 mediates the rapid anti-inflammatory effects of neutrophil-derived microparticles. Blood. 2008;112(6):2512-2519. http://doi:10.1182/blood-2008-02-140533.
  23. McArthur S, Cristante E, Paterno M, Christian H, Roncaroli F, Gillies GE, et al. Annexin A1: a central player in the anti-inflammatory and neuroprotective role of microglia. Journal of Immunology. 2010;185(10):6317-6328. http://doi:10.4049/jimmunol.1001095.
  24. Lachner J, Mlitz V, Tschachler E, Eckhart L. Epidermal cornification is preceded by the expression of a keratinocyte-specific set of pyroptosis-related genes. Scientific Reports. 2017;7(1):17446. http://doi:10.1038/s41598-017-17782-4.
  25. Kambara H, Liu F, Zhang X, Liu P, Bajrami B, Teng Y, et al. Gasdermin D exerts anti-inflammatory effects by promoting neutrophil death. Cell Reports. 2018;22(11):2924-2936. http://doi:10.1016/j.celrep.2018.02.067.
  26. Calixto Fernandes MH, Schricker T, Magder S, Hatzakorzian R. Perioperative fluid management in kidney transplantation: a black box. Critical Care. 2018;22(1):14. http://doi:10.1186/s13054-017-1928-2.
  27. Dimtrakopoulos F-ID, Kottorou A, Yang A, Rodgers K, Baylin S, Hulbert A, et al. Correlation of exosome concentrations in the plasma of lung cancer patients with disease stage. Journal of Clinical Oncology. 2016;34(15_suppl):e23016-e. http://doi:10.1200/JCO.2016.34.15_suppl.e23016.