Skip to main content

Advertisement

SpringerLink
Log in

Association of MicroRNA-223 Expression with Hepatic Ischemia/Reperfusion Injury in Mice

  • Original Article
  • Published:
Digestive Diseases and Sciences Aims and scope Submit manuscript

Abstract

MicroRNAs are a group of small non-coding RNAs with modulator activity of gene expression. Recent studies have uncovered a profound role of microRNAs in liver diseases. This study aimed to investigate a potential relationship between microRNA-223 (miR-223) expression and hepatic ischemia/reperfusion injury in mice. Quantitative RT-PCR analysis showed that miR-223 expression levels were greatly up-regulated in the livers after 75 min ischemia followed by 120 min reperfusion when compared to sham controls (2.59 ± 0.23 vs. 0.83 ± 0.15; P < 0.01). Correlation analysis also revealed that hepatic miR-223 expression level was significantly positively correlated with serum markers of ischemic injury. By prediction assay of miRNA targets mRNA, acyl-CoA synthetase long-chain family member 3, ephrin A1, and ras homolog gene family member B were predicted to be downstream targets of miR-223. Thus, we conclude that hepatic ischemia/reperfusion injury might be another form of liver disease that is associated with alteration in miR-223 expression.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Selzner N, Rudiger H, Graf R, Clavien PA. Protective strategies against ischemic injury of the liver. Gastroenterology. 2003;125:917–936. doi:10.1016/S0016-5085(03)01048-5.

    Article  PubMed  CAS  Google Scholar 

  2. Serracino-Inglott F, Habib NA, Mathie RT. Hepatic ischemia-reperfusion injury. Am J Surg. 2001;181:160–166. doi:10.1016/S0002-9610(00)00573-0.

    Article  PubMed  CAS  Google Scholar 

  3. Xu C, Yu C, Li Y. Current studies on therapeutic approaches for ischemia/reperfusion injury in steatotic livers. Hepatol Res. 2008;38:851–859. doi:10.1111/j.1872-034X.2008.00354.x.

    Article  PubMed  CAS  Google Scholar 

  4. Huguet C, Gavelli A, Bona S. Hepatic resection with ischemia of the liver exceeding one hour. J Am Coll Surg. 1994;178:454–458.

    PubMed  CAS  Google Scholar 

  5. Fondevila C, Busuttil RW, Kupiec-Weglinski JW. Hepatic ischemia/reperfusion injury—a fresh look. Exp Mol Pathol. 2003;74:86–93. doi:10.1016/S0014-4800(03)00008-X.

    Article  PubMed  CAS  Google Scholar 

  6. Busuttil RW, Tanaka K. The utility of marginal donors in liver transplantation. Liver Transpl. 2003;9:651–663. doi:10.1053/jlts.2003.50105.

    Article  PubMed  Google Scholar 

  7. Chan EY, Larson AM, Gernsheimer TB, et al. Recipient and donor factors influence the incidence of graft-vs.-host disease in liver transplant patients. Liver Transpl. 2007;13:516–522. doi:10.1002/lt.21082.

    Article  PubMed  Google Scholar 

  8. Verran D, Kusyk T, Painter D, et al. Clinical experience gained from the use of 120 steatotic donor livers for orthotopic liver transplantation. Liver Transpl. 2003;9:500–505. doi:10.1053/jlts.2003.50099.

    Article  PubMed  Google Scholar 

  9. Banga NR, Homer-Vanniasinkam S, Graham A, Al-Mukhtar A, White SA, Prasad KR. Ischaemic preconditioning in transplantation and major resection of the liver. Br J Surg. 2005;92:528–538. doi:10.1002/bjs.5004.

    Article  PubMed  CAS  Google Scholar 

  10. Defamie V, Cursio R, Le Brigand K, et al. Gene expression profiling of human liver transplants identifies an early transcriptional signature associated with initial poor graft function. Am J Transpl. 2008;8:1221–1236. doi:10.1111/j.1600-6143.2008.02249.x.

    Article  CAS  Google Scholar 

  11. Borozan I, Chen L, Sun J, et al. Gene expression profiling of acute liver stress during living donor liver transplantation. Am J Transpl. 2006;6:806–824. doi:10.1111/j.1600-6143.2006.01254.x.

    Article  CAS  Google Scholar 

  12. Navarro-Sabate A, Peralta C, Calvo MN, et al. Mediators of rat ischemic hepatic preconditioning after cold preservation identified by microarray analysis. Liver Transpl. 2006;12:1615–1625. doi:10.1002/lt.20863.

    Article  PubMed  Google Scholar 

  13. Bartel DP. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell. 2004;116:281–297. doi:10.1016/S0092-8674(04)00045-5.

    Article  PubMed  CAS  Google Scholar 

  14. Budhu A, Jia HL, Forgues M, et al. Identification of metastasis-related microRNAs in hepatocellular carcinoma. Hepatology. 2008;47:897–907. doi:10.1002/hep.22160.

    Article  PubMed  CAS  Google Scholar 

  15. Murakami Y, Yasuda T, Saigo K, et al. Comprehensive analysis of microRNA expression patterns in hepatocellular carcinoma and non-tumorous tissues. Oncogene. 2006;25:2537–2545. doi:10.1038/sj.onc.1209283.

    Article  PubMed  CAS  Google Scholar 

  16. Shan Y, Zheng J, Lambrecht RW, Bonkovsky HL. Reciprocal effects of micro-RNA-122 on expression of heme oxygenase-1 and hepatitis C virus genes in human hepatocytes. Gastroenterology. 2007;133:1166–1174. doi:10.1053/j.gastro.2007.08.002.

    Article  PubMed  CAS  Google Scholar 

  17. Moffat ID, Boutros PC, Celius T, Linden J, Pohjanvirta R, Okey AB. MicroRNAs in adult rodent liver are refractory to dioxin treatment. Toxicol Sci. 2007;99:470–487. doi:10.1093/toxsci/kfm189.

    Article  PubMed  CAS  Google Scholar 

  18. Girard M, Jacquemin E, Munnich A, Lyonnet S, Henrion-Caude A. miR-122, a paradigm for the role of microRNAs in the liver. J Hepatol. 2008;48:648–656. doi:10.1016/j.jhep.2008.01.019.

    Article  PubMed  CAS  Google Scholar 

  19. Fukao T, Fukuda Y, Kiga K, et al. An evolutionarily conserved mechanism for microRNA-223 expression revealed by microRNA gene profiling. Cell. 2007;129:617–631. doi:10.1016/j.cell.2007.02.048.

    Article  PubMed  CAS  Google Scholar 

  20. Johnnidis JB, Harris MH, Wheeler RT, et al. Regulation of progenitor cell proliferation and granulocyte function by microRNA-223. Nature. 2008;451:1125–1129. doi:10.1038/nature06607.

    Article  PubMed  CAS  Google Scholar 

  21. Wong QW, Lung RW, Law PT, et al. MicroRNA-223 is commonly repressed in hepatocellular carcinoma and potentiates expression of Stathmin1. Gastroenterology. 2008;135:257–269. doi:10.1053/j.gastro.2008.04.003.

    Article  PubMed  CAS  Google Scholar 

  22. Xu C, Zhang X, Yu C, Lu G, Chen S, Xu L, Ding W, Shi Q, Li Y. Proteomic analysis of hepatic ischemia/reperfusion injury and ischemic preconditioning in mice revealed the protective role of ATP5β. Proteomics. 2008. (in press). doi:10.1002/pmic.200800393.

  23. Lewis BP, Shih IH, Jones-Rhoades MW, Bartel DP, Burge CB. Prediction of mammalian microRNA targets. Cell. 2003;115:787–798. doi:10.1016/S0092-8674(03)01018-3.

    Article  PubMed  CAS  Google Scholar 

  24. John B, Enright AJ, Aravin A, Tuschl T, Sander C, Marks DS. Human microRNA targets. PLoS Biol. 2004;2:e363. doi:10.1371/journal.pbio.0020363.

    Article  PubMed  CAS  Google Scholar 

  25. Vascotto C, Cesaratto L, D’Ambrosio C, et al. Proteomic analysis of liver tissues subjected to early ischemia/reperfusion injury during human orthotopic liver transplantation. Proteomics. 2006;6:3455–3465. doi:10.1002/pmic.200500770.

    Article  PubMed  CAS  Google Scholar 

  26. Carthew RW. Gene regulation by microRNAs. Curr Opin Genet Dev. 2006;16:203–208. doi:10.1016/j.gde.2006.02.012.

    Article  PubMed  CAS  Google Scholar 

  27. Fukushima T, Hamada Y, Yamada H, Horii I. Changes of micro-RNA expression in rat liver treated by acetaminophen or carbon tetrachloride—regulating role of micro-RNA for RNA expression. J Toxicol Sci. 2007;32:401–409. doi:10.2131/jts.32.401.

    Article  PubMed  CAS  Google Scholar 

  28. Fujimoto Y, Itabe H, Kinoshita T, et al. Involvement of ACSL in local synthesis of neutral lipids in cytoplasmic lipid droplets in human hepatocyte HuH7. J Lipid Res. 2007;48:1280–1292. doi:10.1194/jlr.M700050-JLR200.

    Article  PubMed  CAS  Google Scholar 

  29. Yamashita T, Ohneda K, Nagano M, et al. Hypoxia-inducible transcription factor-2alpha in endothelial cells regulates tumor neovascularization through activation of ephrin A1. J Biol Chem. 2008;283:18926–18936. doi:10.1074/jbc.M709133200.

    Article  PubMed  CAS  Google Scholar 

  30. Kojima I, Tanaka T, Inagi R, et al. Protective role of hypoxia-inducible factor-2alpha against ischemic damage and oxidative stress in the kidney. J Am Soc Nephrol. 2007;18:1218–1226. doi:10.1681/ASN.2006060639.

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

The authors thank Ms. Qiao-Juan Shi for her help in animal experiments and Drs. Li-Ming Xu and Ding Wei for their assistance in histological analysis. This study was supported by the National Natural Science Foundation of China (No. 30571804).

Author information

Authors and Affiliations

  1. Department of Gastroenterology, The First Affiliated Hospital, College of Medicine, Zhejiang University, 79 Qingchun Road, Hangzhou, 310003, China

    Chao-Hui Yu, Cheng-Fu Xu & You-Ming Li

Authors
  1. Chao-Hui Yu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Cheng-Fu Xu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. You-Ming Li
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to You-Ming Li.

Additional information

Chao-Hui Yu and Cheng-Fu Xu contributed equally to this work.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Yu, CH., Xu, CF. & Li, YM. Association of MicroRNA-223 Expression with Hepatic Ischemia/Reperfusion Injury in Mice. Dig Dis Sci 54, 2362–2366 (2009). https://doi.org/10.1007/s10620-008-0629-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10620-008-0629-8

Keywords

Search

Navigation