Expression Pattern of MicroRNA-21 during the Liver Ischemia/Reperfusion
,
Abstract
Ischemia/reperfusion (I/R) injury in cadaveric liver transplantation is not avoidable. Liver I/R injury is an important phenomenon in hepatic damage. MicroRNA-21 (miR-21) plays an important role in I/R injury. The present study aimed to determine the expression pattern of miR-21 in liver I/R injury/recovery and its correlation with the immunologic transmission signals pathways several days post-reperfusion.
In an animal model for I/R in the liver, 40 male Balb/c mice were divided into 3 groups. The animals were monitored for 3 and 24 hours, and also for 4, 7, 14, and 28 days post-reperfusion. Liver tissue damage was assessed by histopathology. The plasma alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and total antioxidant capacity (TAC) levels were measured with enzymatic assays. MiR-21, programmed cell death 4 (PDCD4) mRNA, T-cell-restricted intracellular antigen 1 (TIA1) mRNA, and fas ligand (FASL) mRNA expression levels were measured; using reverse transcription-polymerase chain reaction (RT-PCR) at different times after the reperfusion in liver tissue and blood.
Histopathology and plasma ALT, AST, ALP, and TAC levels confirmed liver damage induced by I/R injury. MiR-21 increased by twofold in the liver tissue and on the inflammatory phase after 24 hours of reperfusion; it then continued to decrease up to day 7 post-reperfusion. Afterward, it continued to rise slightly up to day 14 post-reperfusion. This trend was in parallel with the recovery of the liver damage.
MiR-21 expression level in the liver and blood is a predictor of the extent of I/R injury.
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6. O'connell RM, Rao DS, Chaudhuri AA, Baltimore D. Physiological and pathological roles for microRNAs in the immune system. Nat Rev Immunol. 2010;10(2):111.
7. Song G, Sharma AD, Roll GR, Ng R, Lee AY, Blelloch RH, et al. MicroRNAs control hepatocyte proliferation during liver regeneration. Hepatology. 2010;51(5):1735-43.
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11. Krichevsky AM, Gabriely G. miR‐21: a small multi‐faceted RNA. J Cell Mol Med. 2009;13(1):39-53.
12. van den Akker EK, Dor FJ, IJzermans JN, de Bruin RW. MicroRNAs in kidney transplantation: living up to their expectations? J Transplant. 2015;2015.
13. Jia Z, Lian W, Shi H, Cao C, Han S, Wang K, et al. Ischemic Postconditioning Protects Against Intestinal Ischemia/Reperfusion Injury via the HIF-1α/miR-21 Axis. Sci Rep. 2017;7(1):16190.
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15. Jiang W, Kong L, Ni Q, Lu Y, Ding W, Liu G, et al. miR-146a ameliorates liver ischemia/reperfusion injury by suppressing IRAK1 and TRAF6. PLoS One. 2014;9(7):e101530.
16. Zheng D, Li Z, Wei X, Liu R, Shen A, He D, et al. Role of miR-148a in mitigating hepatic ischemia-reperfusion injury by repressing the TLR4 signaling pathway via targeting CaMKIIα in vivo and in vitro. Cell Physiol Biochem. 2018;49(5):2060-72.
17. Xu X, Kriegel AJ, Jiao X, Liu H, Bai X, Olson J, et al. miR-21 in ischemia/reperfusion injury: a double-edged sword? Physiol Genomics. 2014;46(21):789-97.
18. Wigington CP, Jung J, Rye EA, Belauret SL, Philpot AM, Feng Y, et al. Post-transcriptional regulation of programmed cell death 4 (PDCD4) mRNA by the RNA-binding proteins human antigen R (HuR) and T-cell intracellular antigen 1 (TIA1). J Biol Chem. 2015;290(6):3468-87.
19. Xu Q, Ming Z, Dart AM, Du XJ. Optimizing dosage of ketamine and xylazine in murine echocardiography. Clin Exp Pharmacol Physiol. 2007;34(5‐6):499-507.
20. Abe Y, Hines IN, Zibari G, Pavlick K, Gray L, Kitagawa Y, et al. Mouse model of liver ischemia and reperfusion injury: method for studying reactive oxygen and nitrogen metabolites in vivo. Free Radic Biol Med. 2009;46(1):1-7.
21. Romani F, Vertemati M, Frangi M, Aseni P, Monti R, Codeghini A, et al. Effect of superoxide dismutase on liver ischemia-reperfusion injury in the rat: a biochemical monitoring. Eur Surg Res. 1988;20(5-6):335-40.
22. Kuboki S, Shin T, Huber N, Eismann T, Galloway E, Schuster R, et al. Peroxisome proliferator‐activated receptor‐γ protects against hepatic ischemia/reperfusion injury in mice. Hepatology. 2008;47(1):215-24.
23. Akahori T, Sho M, Hamada K, Suzaki Y, Kuzumoto Y, Nomi T, et al. Importance of peroxisome proliferator-activated receptor-γ in hepatic ischemia/reperfusion injury in mice. J Hepatol. 2007;47(6):784-92.
24. Suzuki S, Toledo-Pereyra LH, Rodriguez FJ, Cejalvo D. Neutrophil infiltration as an important factor in liver ischemia and reperfusion injury. Modulating effects of FK506 and cyclosporine. Transplantation. 1993;55(6):1265-72.
25. Xu X, Kriegel AJ, Liu Y, Usa K, Mladinov D, Liu H, et al. Delayed ischemic preconditioning contributes to renal protection by upregulation of miR-21. Kidney Int. 2012;82(11):1167-75.
26. Jia P, Teng J, Zou J, Fang Y, Zhang X, Bosnjak ZJ, et al. miR-21 contributes to xenon-conferred amelioration of renal ischemia-reperfusion injury in mice. Anesthesiology. 2013;119(3):621-30.
27. Hu H, Jiang W, Xi X, Zou C, Ye Z. MicroRNA-21 attenuates renal ischemia reperfusion injury via targeting caspase signaling in mice. Am J Nephrol. 2014;40(3):215-23.
28. Xu C-f, Yu C-h, Li Y-m. Regulation of hepatic microRNA expression in response to ischemic preconditioning following ischemia/reperfusion injury in mice. OMICS. 2009;13(6):513-20.
29. Datta G, Fuller BJ, Davidson BR. Molecular mechanisms of liver ischemia reperfusion injury: insights from transgenic knockout models. World J Gastroenterol. 2013;19(11):1683-98.
30. Kalogeris T, Baines CP, Krenz M, Korthuis RJ. Cell biology of ischemia/reperfusion injury. Int Rev Cell Mol Biol. 2012;298:229.
31. El-Achkar TM. Modulation of apoptosis by ischemic preconditioning: an emerging role for miR-21. Kidney Int. 2012;82(11):1149-51.
32. Cheng Y, Zhu P, Yang J, Liu X, Dong S, Wang X, et al. Ischaemic preconditioning-regulated miR-21 protects heart against ischaemia/reperfusion injury via anti-apoptosis through its target PDCD4. Cardiovasc Res. 2010;87(3):431-9.
33. Buscaglia LEB, Li Y. Apoptosis and the target genes of miR-21. Chin J Cancer. 2011;30(6):371.
34. Meng F, Henson R, Wehbe–Janek H, Ghoshal K, Jacob ST, Patel T. MicroRNA-21 regulates expression of the PTEN tumor suppressor gene in human hepatocellular cancer. Gastroenterology. 2007;133(2):647-58.
35. Deguine J, Barton GM. MyD88: a central player in innate immune signaling. F1000Prime Rep. 2014;6.
36. Wu H, Neilson JR, Kumar P, Manocha M, Shankar P, Sharp PA, et al. miRNA profiling of naïve, effector and memory CD8 T cells. PLoS One. 2007;2(10):e1020-e.
37. Sheedy FJ, Palsson-McDermott E, Hennessy EJ, Martin C, O'Leary JJ, Ruan Q, et al. Negative regulation of TLR4 via targeting of the proinflammatory tumor suppressor PDCD4 by the microRNA miR-21. Nat Immunol. 2009;11:141.
38. Wei J, Feng L, Li Z, Xu G, Fan X. MicroRNA-21 activates hepatic stellate cells via PTEN/Akt signaling. Biomed Pharmacother. 2013;67(5):387-92.
39. Michelotti GA, Machado MV, Diehl AM. NAFLD, NASH and liver cancer. Nat Rev Gastroenterol Hepatol. 2013;10(11):656.
40. Sayed D, Rane S, Lypowy J, He M, Chen I-Y, Vashistha H, et al. MicroRNA-21 targets Sprouty2 and promotes cellular outgrowths. Mol Biol Cell. 2008;19(8):3272-82.
41. Nastos C, Kalimeris K, Papoutsidakis N, Tasoulis M-K, Lykoudis PM, Theodoraki K, et al. Global consequences of liver ischemia/reperfusion injury. Oxid Med Cell Longev. 2014;2014.
42. Liao Q, Han P, Huang Y, Wu Z, Chen Q, Li S, et al. Potential role of circulating microRNA-21 for hepatocellular carcinoma diagnosis: a meta-analysis. PLoS One. 2015;10(6):e0130677.
43. Xu J, Wu C, Che X, Wang L, Yu D, Zhang T, et al. Circulating MicroRNAs, miR‐21, miR‐122, and miR‐223, in patients with hepatocellular carcinoma or chronic hepatitis. Mol Carcinog. 2011;50(2):136-42.
44. Takahashi K, Yan I, Wen H-J, Patel T. microRNAs in liver disease: from diagnostics to therapeutics. Clin Biochem. 2013;46(10):946-52.
45. Wang J, Chen J, Sen S. MicroRNA as biomarkers and diagnostics. J Cell Physiol. 2016;231(1):25-30.
2. Feng S, Goodrich N, Bragg‐Gresham J, Dykstra D, Punch J, DebRoy M, et al. Characteristics associated with liver graft failure: the concept of a donor risk index. Am J Transplant. 2006;6(4):783-90.
3. Bonaccorsi‐Riani E, Pennycuick A, Londoño MC, Lozano JJ, Benitez C, Sawitzki B, et al. Molecular characterization of acute cellular rejection occurring during intentional immunosuppression withdrawal in liver transplantation. Am J Transplant. 2016;16(2):484-96.
4. García-López J, Brieño-Enríquez MA, Del Mazo J. MicroRNA biogenesis and variability. Biomol Concepts. 2013;4(4):367-80.
5. Bartel DP. MicroRNAs: Genomics, Biogenesis, Mechanism, and Function. Cell. 2004;116(2):281-97.
6. O'connell RM, Rao DS, Chaudhuri AA, Baltimore D. Physiological and pathological roles for microRNAs in the immune system. Nat Rev Immunol. 2010;10(2):111.
7. Song G, Sharma AD, Roll GR, Ng R, Lee AY, Blelloch RH, et al. MicroRNAs control hepatocyte proliferation during liver regeneration. Hepatology. 2010;51(5):1735-43.
8. Wang X, Qian R, Zhang W, Chen S, Jin H, Hu R. MicroRNA‐320 expression in myocardial microvascular endothelial cells and its relationship with insulin‐like growth factor‐1 in type 2 diabetic rats. Clin Exp Pharmacol Physiol. 2009;36(2):181-8.
9. Güçlü A, Koçak C, Koçak FE, Akçılar R, Dodurga Y, Akçılar A, et al. Micro RNA-320 as a novel potential biomarker in renal ischemia reperfusion. Ren Fail. 2016;38(9):1468-75.
10. Kumarswamy R, Volkmann I, Thum T. Regulation and function of miRNA-21 in health and disease. RNA Biol. 2011;8(5):706-13.
11. Krichevsky AM, Gabriely G. miR‐21: a small multi‐faceted RNA. J Cell Mol Med. 2009;13(1):39-53.
12. van den Akker EK, Dor FJ, IJzermans JN, de Bruin RW. MicroRNAs in kidney transplantation: living up to their expectations? J Transplant. 2015;2015.
13. Jia Z, Lian W, Shi H, Cao C, Han S, Wang K, et al. Ischemic Postconditioning Protects Against Intestinal Ischemia/Reperfusion Injury via the HIF-1α/miR-21 Axis. Sci Rep. 2017;7(1):16190.
14. Karakatsanis A, Papaconstantinou I, Gazouli M, Lyberopoulou A, Polymeneas G, Voros D. Expression of microRNAs, miR‐21, miR‐31, miR‐122, miR‐145, miR‐146a, miR‐200c, miR‐221, miR‐222, and miR‐223 in patients with hepatocellular carcinoma or intrahepatic cholangiocarcinoma and its prognostic significance. Mol Carcinog. 2013;52(4):297-303.
15. Jiang W, Kong L, Ni Q, Lu Y, Ding W, Liu G, et al. miR-146a ameliorates liver ischemia/reperfusion injury by suppressing IRAK1 and TRAF6. PLoS One. 2014;9(7):e101530.
16. Zheng D, Li Z, Wei X, Liu R, Shen A, He D, et al. Role of miR-148a in mitigating hepatic ischemia-reperfusion injury by repressing the TLR4 signaling pathway via targeting CaMKIIα in vivo and in vitro. Cell Physiol Biochem. 2018;49(5):2060-72.
17. Xu X, Kriegel AJ, Jiao X, Liu H, Bai X, Olson J, et al. miR-21 in ischemia/reperfusion injury: a double-edged sword? Physiol Genomics. 2014;46(21):789-97.
18. Wigington CP, Jung J, Rye EA, Belauret SL, Philpot AM, Feng Y, et al. Post-transcriptional regulation of programmed cell death 4 (PDCD4) mRNA by the RNA-binding proteins human antigen R (HuR) and T-cell intracellular antigen 1 (TIA1). J Biol Chem. 2015;290(6):3468-87.
19. Xu Q, Ming Z, Dart AM, Du XJ. Optimizing dosage of ketamine and xylazine in murine echocardiography. Clin Exp Pharmacol Physiol. 2007;34(5‐6):499-507.
20. Abe Y, Hines IN, Zibari G, Pavlick K, Gray L, Kitagawa Y, et al. Mouse model of liver ischemia and reperfusion injury: method for studying reactive oxygen and nitrogen metabolites in vivo. Free Radic Biol Med. 2009;46(1):1-7.
21. Romani F, Vertemati M, Frangi M, Aseni P, Monti R, Codeghini A, et al. Effect of superoxide dismutase on liver ischemia-reperfusion injury in the rat: a biochemical monitoring. Eur Surg Res. 1988;20(5-6):335-40.
22. Kuboki S, Shin T, Huber N, Eismann T, Galloway E, Schuster R, et al. Peroxisome proliferator‐activated receptor‐γ protects against hepatic ischemia/reperfusion injury in mice. Hepatology. 2008;47(1):215-24.
23. Akahori T, Sho M, Hamada K, Suzaki Y, Kuzumoto Y, Nomi T, et al. Importance of peroxisome proliferator-activated receptor-γ in hepatic ischemia/reperfusion injury in mice. J Hepatol. 2007;47(6):784-92.
24. Suzuki S, Toledo-Pereyra LH, Rodriguez FJ, Cejalvo D. Neutrophil infiltration as an important factor in liver ischemia and reperfusion injury. Modulating effects of FK506 and cyclosporine. Transplantation. 1993;55(6):1265-72.
25. Xu X, Kriegel AJ, Liu Y, Usa K, Mladinov D, Liu H, et al. Delayed ischemic preconditioning contributes to renal protection by upregulation of miR-21. Kidney Int. 2012;82(11):1167-75.
26. Jia P, Teng J, Zou J, Fang Y, Zhang X, Bosnjak ZJ, et al. miR-21 contributes to xenon-conferred amelioration of renal ischemia-reperfusion injury in mice. Anesthesiology. 2013;119(3):621-30.
27. Hu H, Jiang W, Xi X, Zou C, Ye Z. MicroRNA-21 attenuates renal ischemia reperfusion injury via targeting caspase signaling in mice. Am J Nephrol. 2014;40(3):215-23.
28. Xu C-f, Yu C-h, Li Y-m. Regulation of hepatic microRNA expression in response to ischemic preconditioning following ischemia/reperfusion injury in mice. OMICS. 2009;13(6):513-20.
29. Datta G, Fuller BJ, Davidson BR. Molecular mechanisms of liver ischemia reperfusion injury: insights from transgenic knockout models. World J Gastroenterol. 2013;19(11):1683-98.
30. Kalogeris T, Baines CP, Krenz M, Korthuis RJ. Cell biology of ischemia/reperfusion injury. Int Rev Cell Mol Biol. 2012;298:229.
31. El-Achkar TM. Modulation of apoptosis by ischemic preconditioning: an emerging role for miR-21. Kidney Int. 2012;82(11):1149-51.
32. Cheng Y, Zhu P, Yang J, Liu X, Dong S, Wang X, et al. Ischaemic preconditioning-regulated miR-21 protects heart against ischaemia/reperfusion injury via anti-apoptosis through its target PDCD4. Cardiovasc Res. 2010;87(3):431-9.
33. Buscaglia LEB, Li Y. Apoptosis and the target genes of miR-21. Chin J Cancer. 2011;30(6):371.
34. Meng F, Henson R, Wehbe–Janek H, Ghoshal K, Jacob ST, Patel T. MicroRNA-21 regulates expression of the PTEN tumor suppressor gene in human hepatocellular cancer. Gastroenterology. 2007;133(2):647-58.
35. Deguine J, Barton GM. MyD88: a central player in innate immune signaling. F1000Prime Rep. 2014;6.
36. Wu H, Neilson JR, Kumar P, Manocha M, Shankar P, Sharp PA, et al. miRNA profiling of naïve, effector and memory CD8 T cells. PLoS One. 2007;2(10):e1020-e.
37. Sheedy FJ, Palsson-McDermott E, Hennessy EJ, Martin C, O'Leary JJ, Ruan Q, et al. Negative regulation of TLR4 via targeting of the proinflammatory tumor suppressor PDCD4 by the microRNA miR-21. Nat Immunol. 2009;11:141.
38. Wei J, Feng L, Li Z, Xu G, Fan X. MicroRNA-21 activates hepatic stellate cells via PTEN/Akt signaling. Biomed Pharmacother. 2013;67(5):387-92.
39. Michelotti GA, Machado MV, Diehl AM. NAFLD, NASH and liver cancer. Nat Rev Gastroenterol Hepatol. 2013;10(11):656.
40. Sayed D, Rane S, Lypowy J, He M, Chen I-Y, Vashistha H, et al. MicroRNA-21 targets Sprouty2 and promotes cellular outgrowths. Mol Biol Cell. 2008;19(8):3272-82.
41. Nastos C, Kalimeris K, Papoutsidakis N, Tasoulis M-K, Lykoudis PM, Theodoraki K, et al. Global consequences of liver ischemia/reperfusion injury. Oxid Med Cell Longev. 2014;2014.
42. Liao Q, Han P, Huang Y, Wu Z, Chen Q, Li S, et al. Potential role of circulating microRNA-21 for hepatocellular carcinoma diagnosis: a meta-analysis. PLoS One. 2015;10(6):e0130677.
43. Xu J, Wu C, Che X, Wang L, Yu D, Zhang T, et al. Circulating MicroRNAs, miR‐21, miR‐122, and miR‐223, in patients with hepatocellular carcinoma or chronic hepatitis. Mol Carcinog. 2011;50(2):136-42.
44. Takahashi K, Yan I, Wen H-J, Patel T. microRNAs in liver disease: from diagnostics to therapeutics. Clin Biochem. 2013;46(10):946-52.
45. Wang J, Chen J, Sen S. MicroRNA as biomarkers and diagnostics. J Cell Physiol. 2016;231(1):25-30.
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| Issue | Vol 20 No 1 (2021) | |
| Section | Original Article(s) | |
| DOI | https://doi.org/10.18502/ijaai.v20i1.5415 | |
| Keywords | ||
| Ischemia Liver Mice MicroRNA-21 Reperfusion | ||
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How to Cite
1.
Salah A, Karimi MH, Sajedianfard J, Nazifi S, Yaghobi R. Expression Pattern of MicroRNA-21 during the Liver Ischemia/Reperfusion. Iran J Allergy Asthma Immunol. 2021;20(1):88-97.
