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http://dx.doi.org/10.4062/biomolther.2016.174

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)
Publication Information
Biomolecules & Therapeutics / v.25, no.4, 2017 , pp. 367-373 More about this Journal
Abstract
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.
Keywords
miRNAs; Exosomes; Liver-specific injury; N-acetyl cysteine; Biomarkers;
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1 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.   DOI
2 Etheridge, A., Lee, I., Hood, L., Galas, D. and Wang, K. (2011) Extracellular microRNA: a new source of biomarkers. Mutat. Res. 717, 85-90.   DOI
3 Faraoni, I., Antonetti, F. R., Cardone, J. and Bonmassar, E. (2009) miR-155 gene: a typical multifunctional microRNA. Biochim. Biophys. Acta 1792, 497-505.   DOI
4 Guay, C. and Regazzi, R. (2013) Circulating microRNAs as novel biomarkers for diabetes mellitus. Nat. Rev. Endocrinol. 9, 513-521.   DOI
5 Hinson, J. A., Roberts, D. W. and James, L. P. (2010) Mechanisms of acetaminophen-induced liver necrosis. Handb. Exp. Pharmacol. (196), 369-405.
6 Hu, G., Drescher, K. M. and Chen, X. M. (2012) Exosomal miRNAs: biological properties and therapeutic potential. Front. Genet. 3, 56.
7 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.   DOI
8 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.   DOI
9 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.   DOI
10 Kaplowitz, N. (2005) Idiosyncratic drug hepatotoxicity. Nat. Rev. Drug Discov. 4, 489-499.   DOI
11 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.   DOI
12 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.   DOI
13 Ohno, S., Ishikawa, A. and Kuroda, M. (2013) Roles of exosomes and microvesicles in disease pathogenesis. Adv. Drug Deliv. Rev. 65, 398-401.   DOI
14 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.   DOI
15 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.   DOI
16 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.   DOI
17 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.   DOI
18 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.   DOI
19 Turchinovich, A., Weiz, L., Langheinz, A. and Burwinkel, B. (2011) Characterization of extracellular circulating microRNA. Nucleic Acids Res. 39, 7223-7233.   DOI
20 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.   DOI
21 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.   DOI
22 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.   DOI
23 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.   DOI
24 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.   DOI
25 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.   DOI
26 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.   DOI
27 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.   DOI
28 Boots, A. W., Haenen, G. R. and Bast, A. (2008) Health effects of quercetin: from antioxidant to nutraceutical. Eur. J. Pharmacol. 585, 325-337.   DOI
29 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.
30 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.
31 Miller, R. P., Tadagavadi, R. K., Ramesh, G. and Reeves, W. B. (2010) Mechanisms of Cisplatin nephrotoxicity. Toxins (Basel) 2, 2490-2518.   DOI
32 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.   DOI
33 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.   DOI
34 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.   DOI
35 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.   DOI