Journal of Veterinary Science

The Korean Society of Veterinary Science (대한수의학회)
권호 표지
DOI QR코드

DOI QR Code

Identification of urinary microRNA biomarkers for in vivo gentamicin-induced nephrotoxicity models

  • Jeon, Byung-Suk (Toxicological Evaluation Laboratory, Animal and Plant Quarantine Agency) ;
  • Lee, Soo-ho (Toxicological Evaluation Laboratory, Animal and Plant Quarantine Agency) ;
  • Hwang, So-Ryeon (Toxicological Evaluation Laboratory, Animal and Plant Quarantine Agency) ;
  • Yi, Hee (Toxicological Evaluation Laboratory, Animal and Plant Quarantine Agency) ;
  • Bang, Ji-Hyun (Toxicological Evaluation Laboratory, Animal and Plant Quarantine Agency) ;
  • Tham, Nga Thi Thu (Toxicological Evaluation Laboratory, Animal and Plant Quarantine Agency) ;
  • Lee, Hyun-Kyoung (Animal Pathodiagnostic Laboratory, Animal and Plant Quarantine Agency) ;
  • Woo, Gye-Hyeong (Department of Clinical Laboratory Science, Semyung University) ;
  • Kang, Hwan-Goo (Department of Clinical Laboratory Science, Semyung University) ;
  • Ku, Hyun-Ok (Toxicological Evaluation Laboratory, Animal and Plant Quarantine Agency)
  • Received : 2020.04.30
  • Accepted : 2020.09.07
  • Published : 2020.11.30
Download PDF
⟨ Previous Next ⟩

Abstract

Background: Although previous in vivo studies explored urinary microRNA (miRNA), there is no agreement on nephrotoxicity-specific miRNA biomarkers. Objectives: In this study, we assessed whether urinary miRNAs could be employed as biomarkers for nephrotoxicity. Methods: For this, literature-based candidate miRNAs were identified by reviewing the previous studies. Female Sprague-Dawley rats received subcutaneous injections of a single dose or repeated doses (3 consecutive days) of gentamicin (GEN; 137 or 412 mg/kg). The expression of miRNAs was analyzed by real-time reverse transcription-polymerase chain reaction in 16 h pooled urine from GEN-treated rats. Results: GEN-induced acute kidney injury was confirmed by the presence of tubular necrosis. We identified let-7g-5p, miR-21-3p, 26b-3p, 192-5p, and 378a-3p significantly upregulated in the urine of GEN-treated rats with the appearance of the necrosis in proximal tubules. Specifically, miR-26-3p, 192-5p, and 378a-3p with highly expressed levels in urine of rats with GEN-induced acute tubular injury were considered to have sensitivities comparable to clinical biomarkers, such as blood urea nitrogen, serum creatinine, and urinary kidney injury molecule protein. Conclusions: These results indicated the potential involvement of urinary miRNAs in chemical-induced nephrotoxicity, suggesting that certain miRNAs could serve as biomarkers for acute nephrotoxicity.

Keywords

Acknowledgement

This study was supported by a grant from the Animal and Plant Quarantine Agency.

References

  1. Edelstein CL. Biomarkers of acute kidney injury. Adv Chronic Kidney Dis. 2008;15(3):222-234. https://doi.org/10.1053/j.ackd.2008.04.003
  2. Pavkovic M, Robinson-Cohen C, Chua AS, Nicoara O, Cardenas-Gonzalez M, Bijol V, et al. Detection of drug-induced acute kidney injury in humans using urinary KIM-1, miR-21, -200c and -423. Toxicol Sci. 2016;152(1):205-213. https://doi.org/10.1093/toxsci/kfw077
  3. Kanki M, Moriguchi A, Sasaki D, Mitori H, Yamada A, Unami A, et al. Identification of urinary miRNA biomarkers for detecting cisplatin-induced proximal tubular injury in rats. Toxicology. 2014;324:158-168. https://doi.org/10.1016/j.tox.2014.05.004
  4. Nassirpour R, Mathur S, Gosink MM, Li Y, Shoieb AM, Wood J, et al. Identification of tubular injury microRNA biomarkers in urine: comparison of next-generation sequencing and qPCR-based profiling platforms. BMC Genomics. 2014;15(1):485. https://doi.org/10.1186/1471-2164-15-485
  5. Pavkovic M, Riefke B, Ellinger-Ziegelbauer H. Urinary microRNA profiling for identification of biomarkers after cisplatin-induced kidney injury. Toxicology. 2014;324:147-157. https://doi.org/10.1016/j.tox.2014.05.005
  6. Wolenski FS, Shah P, Sano T, Shinozawa T, Bernard H, Gallacher MJ, et al. Identification of microRNA biomarker candidates in urine and plasma from rats with kidney or liver damage. J Appl Toxicol. 2017;37(3):278-286. https://doi.org/10.1002/jat.3358
  7. Zhou X, Qu Z, Zhu C, Lin Z, Huo Y, Wang X, et al. Identification of urinary microRNA biomarkers for detection of gentamicin-induced acute kidney injury in rats. Regul Toxicol Pharmacol. 2016;78:78-84. https://doi.org/10.1016/j.yrtph.2016.04.001
  8. Bartel DP. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell. 2004;116(2):281-297. https://doi.org/10.1016/S0092-8674(04)00045-5
  9. Lagos-Quintana M, Rauhut R, Lendeckel W, Tuschl T. Identification of novel genes coding for small expressed RNAs. Science. 2001;294(5543):853-858. https://doi.org/10.1126/science.1064921
  10. Guo Z, Maki M, Ding R, Yang Y, Zhang B, Xiong L. Genome-wide survey of tissue-specific microRNA and transcription factor regulatory networks in 12 tissues. Sci Rep. 2014;4(1):5150. https://doi.org/10.1038/srep05150
  11. Lagos-Quintana M, Rauhut R, Yalcin A, Meyer J, Lendeckel W, Tuschl T. Identification of tissue-specific microRNAs from mouse. Curr Biol. 2002;12(9):735-739. https://doi.org/10.1016/S0960-9822(02)00809-6
  12. Zhou M, Hara H, Dai Y, Mou L, Cooper DK, Wu C, et al. Circulating organ-specific microRNAs serve as biomarkers in organ-specific diseases: implications for organ allo- and xeno-transplantation. Int J Mol Sci. 2016;17(8):E1232.
  13. Chen X, Ba Y, Ma L, Cai X, Yin Y, Wang K, et al. Characterization of microRNAs in serum: a novel class of biomarkers for diagnosis of cancer and other diseases. Cell Res. 2008;18(10):997-1006. https://doi.org/10.1038/cr.2008.282
  14. Mitchell PS, Parkin RK, Kroh EM, Fritz BR, Wyman SK, Pogosova-Agadjanyan EL, et al. Circulating microRNAs as stable blood-based markers for cancer detection. Proc Natl Acad Sci U S A. 2008;105(30):10513-10518. https://doi.org/10.1073/pnas.0804549105
  15. Hwang SR, Tham NTT, Lee SH, Bang JH, Yi H, Park YI, et al. Comparison of microRNA expressions for the identification of chemical hazards in in vivo and in vitro hepatic injury models. J Appl Toxicol. 2019;39(2):333-342. https://doi.org/10.1002/jat.3722
  16. Selby NM, Shaw S, Woodier N, Fluck RJ, Kolhe NV. Gentamicin-associated acute kidney injury. QJM. 2009;102(12):873-880. https://doi.org/10.1093/qjmed/hcp143
  17. World Health Organization. Gentamicin (WHO food additives series 34) [Internet]. Geneva: World Health Organization; http://www.inchem.org/documents/jecfa/jecmono/v041je05.htm. Updated 1988.
  18. Quiros Y, Vicente-Vicente L, Morales AI, Lopez-Novoa JM, Lopez-Hernandez FJ. An integrative overview on the mechanisms underlying the renal tubular cytotoxicity of gentamicin. Toxicol Sci. 2011;119(2):245-256. https://doi.org/10.1093/toxsci/kfq267
  19. Kagawa T, Zarybnicky T, Omi T, Shirai Y, Toyokuni S, Oda S, et al. A scrutiny of circulating microRNA biomarkers for drug-induced tubular and glomerular injury in rats. Toxicology. 2019;415:26-36. https://doi.org/10.1016/j.tox.2019.01.011
  20. Hara T, Koyama K, Miyazaki H, Ohguro Y, Shimizu M. Safety evaluation of KW-1062. I. Acute toxicity in mice, rats and dogs, subacute and chronic toxicity in rats (author's transl). Jpn J Antibiot. 1977;30(6):386-407.
  21. Ichii O, Horino T. MicroRNAs associated with the development of kidney diseases in humans and animals. J Toxicol Pathol. 2018;31(1):23-34. https://doi.org/10.1293/tox.2017-0051
  22. Li YF, Jing Y, Hao J, Frankfort NC, Zhou X, Shen B, et al. MicroRNA-21 in the pathogenesis of acute kidney injury. Protein Cell. 2013;4(11):813-819. https://doi.org/10.1007/s13238-013-3085-y
  23. Sun Y, Koo S, White N, Peralta E, Esau C, Dean NM, et al. Development of a micro-array to detect human and mouse microRNAs and characterization of expression in human organs. Nucleic Acids Res. 2004;32(22):e188. https://doi.org/10.1093/nar/gnh186
  24. Tian Z, Greene AS, Pietrusz JL, Matus IR, Liang M. MicroRNA-target pairs in the rat kidney identified by microRNA microarray, proteomic, and bioinformatic analysis. Genome Res. 2008;18(3):404-411. https://doi.org/10.1101/gr.6587008
  25. Zhang C, Ma P, Zhao Z, Jiang N, Lian D, Huo P, et al. MiRNA-mRNA regulatory network analysis of mesenchymal stem cell treatment in cisplatin-induced acute kidney injury identifies roles for miR-210/Serpine1 and miR-378/Fos in regulating inflammation. Mol Med Rep. 2019;20(2):1509-1522.