DOI QR코드

DOI QR Code

Circulating Plasma and Exosomal microRNAs as Indicators of Drug-Induced Organ Injury in Rodent Models

  • Cho, Young-Eun (Department of Molecular Medicine, CMRI, School of Medicine, Kyungpook National University) ;
  • Kim, Sang-Hyun (Department of Pharmacology, CMRI, School of Medicine, Kyungpook National University) ;
  • Lee, Byung-Heon (Department of Biochemistry and Cell Biology, CMRI, School of Medicine, Kyungpook National University) ;
  • Baek, Moon-Chang (Department of Molecular Medicine, CMRI, School of Medicine, Kyungpook National University)
  • 투고 : 2016.08.04
  • 심사 : 2016.12.13
  • 발행 : 2017.07.01

초록

This study was performed to evaluate whether microRNAs (miRNAs) in circulating exosomes may serve as biomarkers of drug-induced liver, kidney, or muscle-injury. Quantitative PCR analyses were performed to measure the amounts of liver-specific miRNAs (miR-122, miR-192, and miR-155), kidney-specific miR-146a, or muscle-specific miR-206 in plasma and exosomes from mice treated with liver, kidney or muscle toxicants. The levels of liver-specific miRNAs in circulating plasma and exosomes were elevated in acetaminophen-induced liver injury and returned to basal levels by treatment with antioxidant N-acetyl-cysteine. Circulating miR-146a and miR-206 were increased in cisplatin-induced nephrotoxicity and bupivacaine-induced myotoxicity, respectively. Taken together, these results indicate that circulating plasma and exosomal miRNAs can be used as potential biomarkers specific for drug-induced liver, kidney or muscle injury.

키워드

참고문헌

  1. Ason, B., Darnell, D. K., Wittbrodt, B., Berezikov, E., Kloosterman, W. P., Wittbrodt, J., Antin, P. B. and Plasterk, R. H. (2006) Differences in vertebrate microRNA expression. Proc. Natl. Acad. Sci. U.S.A. 103, 14385-14389. https://doi.org/10.1073/pnas.0603529103
  2. Bala, S., Petrasek, J., Mundkur, S., Catalano, D., Levin, I., Ward, J., Alao, H., Kodys, K. and Szabo, G. (2012) Circulating microRNAs in exosomes indicate hepatocyte injury and inflammation in alcoholic, drug-induced, and inflammatory liver diseases. Hepatology 56, 1946-1957. https://doi.org/10.1002/hep.25873
  3. Boots, A. W., Haenen, G. R. and Bast, A. (2008) Health effects of quercetin: from antioxidant to nutraceutical. Eur. J. Pharmacol. 585, 325-337. https://doi.org/10.1016/j.ejphar.2008.03.008
  4. Cho, Y. E., Singh, T. S., Lee, H. C., Moon, P. G., Lee, J. E., Lee, M. H., Choi, E. C., Chen, Y. J., Kim, S. H. and Baek, M. C. (2012) In-depth identification of pathways related to cisplatin-induced hepatotoxicity through an integrative method based on an informatics-assisted label-free protein quantitation and microarray gene expression approach. Mol. Cell Proteomics 11, M111.010884.
  5. Chun, L. J., Tong, M. J., Busuttil, R. W. and Hiatt, J. R. (2009) Acetaminophen hepatotoxicity and acute liver failure. J. Clin. Gastroenterol. 43, 342-349. https://doi.org/10.1097/MCG.0b013e31818a3854
  6. Etheridge, A., Lee, I., Hood, L., Galas, D. and Wang, K. (2011) Extracellular microRNA: a new source of biomarkers. Mutat. Res. 717, 85-90. https://doi.org/10.1016/j.mrfmmm.2011.03.004
  7. Faraoni, I., Antonetti, F. R., Cardone, J. and Bonmassar, E. (2009) miR-155 gene: a typical multifunctional microRNA. Biochim. Biophys. Acta 1792, 497-505. https://doi.org/10.1016/j.bbadis.2009.02.013
  8. Guay, C. and Regazzi, R. (2013) Circulating microRNAs as novel biomarkers for diabetes mellitus. Nat. Rev. Endocrinol. 9, 513-521. https://doi.org/10.1038/nrendo.2013.86
  9. Hinson, J. A., Roberts, D. W. and James, L. P. (2010) Mechanisms of acetaminophen-induced liver necrosis. Handb. Exp. Pharmacol. (196), 369-405.
  10. Hu, G., Drescher, K. M. and Chen, X. M. (2012) Exosomal miRNAs: biological properties and therapeutic potential. Front. Genet. 3, 56.
  11. Huang, Y., Liu, Y., Li, L., Su, B., Yang, L., Fan, W., Yin, Q., Chen, L., Cui, T., Zhang, J., Lu, Y., Cheng, J., Fu, P. and Liu, F. (2014) Involvement of inflammation-related miR-155 and miR-146a in diabetic nephropathy: implications for glomerular endothelial injury. BMC Nephrol. 15, 142. https://doi.org/10.1186/1471-2369-15-142
  12. Ichii, O., Otsuka, S., Sasaki, N., Namiki, Y., Hashimoto, Y. and Kon, Y. (2012) Altered expression of microRNA miR-146a correlates with the development of chronic renal inflammation. Kidney Int. 81, 280-292. https://doi.org/10.1038/ki.2011.345
  13. John, K., Hadem, J., Krech, T., Wahl, K., Manns, M. P., Dooley, S., Batkai, S., Thum, T., Schulze-Osthoff, K. and Bantel, H. (2014) MicroRNAs play a role in spontaneous recovery from acute liver failure. Hepatology 60, 1346-1355. https://doi.org/10.1002/hep.27250
  14. Kaplowitz, N. (2005) Idiosyncratic drug hepatotoxicity. Nat. Rev. Drug Discov. 4, 489-499. https://doi.org/10.1038/nrd1750
  15. Lagos-Quintana, M., Rauhut, R., Yalcin, A., Meyer, J., Lendeckel, W. and Tuschl, T. (2002) Identification of tissue-specific microRNAs from mouse. Curr. Biol. 12, 735-739.
  16. Liu, N., Williams, A. H., Maxeiner, J. M., Bezprozvannaya, S., Shelton, J. M., Richardson, J. A., Bassel-Duby, R. and Olson, E. N. (2012) microRNA-206 promotes skeletal muscle regeneration and delays progression of Duchenne muscular dystrophy in mice. J. Clin. Invest. 122, 2054-2065. https://doi.org/10.1172/JCI62656
  17. Miller, R. P., Tadagavadi, R. K., Ramesh, G. and Reeves, W. B. (2010) Mechanisms of Cisplatin nephrotoxicity. Toxins (Basel) 2, 2490-2518. https://doi.org/10.3390/toxins2112490
  18. Mizuno, H., Nakamura, A., Aoki, Y., Ito, N., Kishi, S., Yamamoto, K., Sekiguchi, M., Takeda, S. and Hashido, K. (2011) Identification of muscle-specific microRNAs in serum of muscular dystrophy animal models: promising novel blood-based markers for muscular dystrophy. PLoS ONE 6, e18388. https://doi.org/10.1371/journal.pone.0018388
  19. Morales, A. I., Vicente-Sanchez, C., Jerkic, M., Santiago, J. M., Sanchez-Gonzalez, P. D., Perez-Barriocanal, F. and Lopez-Novoa, J. M. (2006a) Effect of quercetin on metallothionein, nitric oxide synthases and cyclooxygenase-2 expression on experimental chronic cadmium nephrotoxicity in rats. Toxicol. Appl. Pharmacol. 210, 128-135. https://doi.org/10.1016/j.taap.2005.09.006
  20. Morales, A. I., Vicente-Sanchez, C., Sandoval, J. M., Egido, J., Mayoral, P., Arevalo, M. A., Fernandez-Tagarro, M., Lopez-Novoa, J. M. and Perez-Barriocanal, F. (2006b) Protective effect of quercetin on experimental chronic cadmium nephrotoxicity in rats is based on its antioxidant properties. Food Chem. Toxicol. 44, 2092-2100. https://doi.org/10.1016/j.fct.2006.07.012
  21. Nakasa, T., Ishikawa, M., Shi, M., Shibuya, H., Adachi, N. and Ochi, M. (2010) Acceleration of muscle regeneration by local injection of muscle-specific microRNAs in rat skeletal muscle injury model. J. Cell. Mol. Med. 14, 2495-2505. https://doi.org/10.1111/j.1582-4934.2009.00898.x
  22. Nonaka, I., Takagi, A., Ishiura, S., Nakase, H. and Sugita, H. (1983) Pathophysiology of muscle fiber necrosis induced by bupivacaine hydrochloride (Marcaine). Acta Neuropathol. 60, 167-174. https://doi.org/10.1007/BF00691863
  23. Ohno, S., Ishikawa, A. and Kuroda, M. (2013) Roles of exosomes and microvesicles in disease pathogenesis. Adv. Drug Deliv. Rev. 65, 398-401. https://doi.org/10.1016/j.addr.2012.07.019
  24. Sanchez-Gonzalez, P. D., Lopez-Hernandez, F. J., Perez-Barriocanal, F., Morales, A. I. and Lopez-Novoa, J. M. (2011) Quercetin reduces cisplatin nephrotoxicity in rats without compromising its anti-tumour activity. Nephrol. Dial. Transplant. 26, 3484-3495. https://doi.org/10.1093/ndt/gfr195
  25. Sempere, L. F., Freemantle, S., Pitha-Rowe, I., Moss, E., Dmitrovsky, E. and Ambros, V. (2004) Expression profiling of mammalian microRNAs uncovers a subset of brain-expressed microRNAs with possible roles in murine and human neuronal differentiation. Genome Biol. 5, R13. https://doi.org/10.1186/gb-2004-5-3-r13
  26. Starkey Lewis, P. J., Dear, J., Platt, V., Simpson, K. J., Craig, D. G., Antoine, D. J., French, N. S., Dhaun, N., Webb, D. J., Costello, E. M., Neoptolemos, J. P., Moggs, J., Goldring, C. E. and Park, B. K. (2011) Circulating microRNAs as potential markers of human druginduced liver injury. Hepatology 54, 1767-1776. https://doi.org/10.1002/hep.24538
  27. Taganov, K. D., Boldin, M. P., Chang, K. J. and Baltimore, D. (2006) NF-${\kappa}B$-dependent induction of microRNA miR-146, an inhibitor targeted to signaling proteins of innate immune responses. Proc. Natl. Acad. Sci. U.S.A. 103, 12481-12486. https://doi.org/10.1073/pnas.0605298103
  28. Toivonen, J. M., Manzano, R., Olivan, S., Zaragoza, P., Garcia-Redondo, A. and Osta, R. (2014) MicroRNA-206: a potential circulating biomarker candidate for amyotrophic lateral sclerosis. PLoS ONE 9, e89065. https://doi.org/10.1371/journal.pone.0089065
  29. Turchinovich, A., Weiz, L., Langheinz, A. and Burwinkel, B. (2011) Characterization of extracellular circulating microRNA. Nucleic Acids Res. 39, 7223-7233. https://doi.org/10.1093/nar/gkr254
  30. Wang, G., Kwan, B. C., Lai, F. M., Chow, K. M., Li, P. K. and Szeto, C. C. (2011) Elevated levels of miR-146a and miR-155 in kidney biopsy and urine from patients with IgA nephropathy. Dis. Markers 30, 171-179. https://doi.org/10.1155/2011/304852
  31. Wang, K., Zhang, S., Marzolf, B., Troisch, P., Brightman, A., Hu, Z., Hood, L. E. and Galas, D. J. (2009) Circulating microRNAs, potential biomarkers for drug-induced liver injury. Proc. Natl. Acad. Sci. U.S.A. 106, 4402-4407. https://doi.org/10.1073/pnas.0813371106
  32. Ward, J., Kanchagar, C., Veksler-Lublinsky, I., Lee, R. C., McGill, M. R., Jaeschke, H., Curry, S. C. and Ambros, V. R. (2014) Circulating microRNA profiles in human patients with acetaminophen hepatotoxicity or ischemic hepatitis. Proc. Natl. Acad. Sci. U.S.A. 111, 12169-12174. https://doi.org/10.1073/pnas.1412608111
  33. Williams, A. H., Valdez, G., Moresi, V., Qi, X., McAnally, J., Elliott, J. L., Bassel-Duby, R., Sanes, J. R. and Olson, E. N. (2009) MicroRNA-206 delays ALS progression and promotes regeneration of neuromuscular synapses in mice. Science 326, 1549-1554. https://doi.org/10.1126/science.1181046
  34. Yu, D. C., Li, Q. G., Ding, X. W. and Ding, Y. T. (2011) Circulating microRNAs: potential biomarkers for cancer. Int. J. Mol. Sci. 12, 2055-2063. https://doi.org/10.3390/ijms12032055
  35. Zhang, Y., Jia, Y., Zheng, R., Guo, Y., Wang, Y., Guo, H., Fei, M. and Sun, S. (2010) Plasma microRNA-122 as a biomarker for viral-, alcohol-, and chemical-related hepatic diseases. Clin. Chem. 56, 1830-1838. https://doi.org/10.1373/clinchem.2010.147850

피인용 문헌

  1. Biomarkers of drug-induced kidney injury vol.23, pp.6, 2017, https://doi.org/10.1097/MCC.0000000000000464
  2. Exosomal microRNAs as potential circulating biomarkers in gastrointestinal tract cancers: a systematic review protocol vol.6, pp.1, 2017, https://doi.org/10.1186/s13643-017-0624-2
  3. Latest advances in diagnosing and predicting DILI: what was new in 2017? vol.12, pp.10, 2018, https://doi.org/10.1080/17474124.2018.1512854
  4. Exogenous exosomes from mice with acetaminophen-induced liver injury promote toxicity in the recipient hepatocytes and mice vol.8, pp.1, 2018, https://doi.org/10.1038/s41598-018-34309-7
  5. Comparison of microRNA expressions for the identification of chemical hazards in in vivo and in vitro hepatic injury models pp.0260437X, 2018, https://doi.org/10.1002/jat.3722
  6. miR-374a Regulates Inflammatory Response in Diabetic Nephropathy by Targeting MCP-1 Expression vol.9, pp.1663-9812, 2018, https://doi.org/10.3389/fphar.2018.00900
  7. The diagnostic role of miR-122 in drug-induced liver injury vol.97, pp.49, 2018, https://doi.org/10.1097/MD.0000000000013478
  8. Extracellular vesicles: Future diagnostic and therapeutic tools for liver disease and regeneration vol.39, pp.10, 2019, https://doi.org/10.1111/liv.14189
  9. Exosomes: Emerging Therapy Delivery Tools and Biomarkers for Kidney Diseases vol.2021, pp.None, 2017, https://doi.org/10.1155/2021/7844455
  10. The Immunological Mechanisms and Immune-Based Biomarkers of Drug-Induced Liver Injury vol.12, pp.None, 2017, https://doi.org/10.3389/fphar.2021.723940
  11. MicroRNAs in toxic acute kidney injury: Systematic scoping review of the current status vol.9, pp.2, 2021, https://doi.org/10.1002/prp2.695
  12. Biomarkers of drug-induced liver injury: a mechanistic perspective through acetaminophen hepatotoxicity vol.15, pp.4, 2021, https://doi.org/10.1080/17474124.2021.1857238
  13. Epigenetic Mechanisms Involved in Cisplatin-Induced Nephrotoxicity: An Update vol.14, pp.6, 2021, https://doi.org/10.3390/ph14060491
  14. Mesenchymal Stem Cell-Derived Exosomes: Applications in Regenerative Medicine vol.10, pp.8, 2017, https://doi.org/10.3390/cells10081959
  15. Role of MicroRNA-155 in Triptolide-induced hepatotoxicity via the Nrf2-Dependent pathway vol.281, pp.None, 2021, https://doi.org/10.1016/j.jep.2021.114489
  16. Dysregulated MicroRNAs as Biomarkers or Therapeutic Targets in Cisplatin-Induced Nephrotoxicity: A Systematic Review vol.22, pp.23, 2017, https://doi.org/10.3390/ijms222312765
  17. Extracellular vesicles in inflammation: Focus on the microRNA cargo of EVs in modulation of liver diseases vol.111, pp.1, 2017, https://doi.org/10.1002/jlb.3mir0321-156r