LncRNA-Airn alleviates acute liver injury by inhibiting hepatocyte apoptosis via the NF-κB signaling pathway.

Shuai Shao, Yu Zhang, Feng Zhou, Xiaoxiang Meng, Zhenjun Yu, Guantong Li, Lina Zheng, Kun Zhang, Yuhan Li, Beichen Guo, Qi Liu, Mengxia Zhang, Xiaoxiao Du, Wei Hong, Tao Han
Author Information
  1. Shuai Shao: The School of Medicine, Nankai University, Tianjin 300071, China.
  2. Yu Zhang: Department of Hepatology and Gastroenterology, the Third Central Clinical College of Tianjin Medical University; Department of Histology and Embryology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300121, China.
  3. Feng Zhou: Department of Hepatology and Gastroenterology, the Third Central Clinical College of Tianjin Medical University; Department of Histology and Embryology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300121, China.
  4. Xiaoxiang Meng: Department of Histology and Embryology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300121, China.
  5. Zhenjun Yu: Department of Hepatology and Gastroenterology, the Third Central Clinical College of Tianjin Medical University; Department of Histology and Embryology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300121, China.
  6. Guantong Li: Department of Hepatology and Gastroenterology, the Third Central Clinical College of Tianjin Medical University; Department of Histology and Embryology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300121, China.
  7. Lina Zheng: Department of Histology and Embryology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300121, China.
  8. Kun Zhang: Department of Histology and Embryology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300121, China.
  9. Yuhan Li: Department of Hepatology and Gastroenterology, the Third Central Clinical College of Tianjin Medical University; Department of Histology and Embryology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300121, China.
  10. Beichen Guo: Department of Hepatology and Gastroenterology, the Third Central Clinical College of Tianjin Medical University; Department of Histology and Embryology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300121, China.
  11. Qi Liu: Department of Histology and Embryology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300121, China.
  12. Mengxia Zhang: Department of Histology and Embryology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300121, China.
  13. Xiaoxiao Du: Department of Histology and Embryology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300121, China.
  14. Wei Hong: Department of Histology and Embryology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300121, China.
  15. Tao Han: The School of Medicine, Nankai University, Tianjin 300071, China.

Abstract

acute liver injury is a common and serious syndrome caused by multiple factors and unclear pathogenesis. If the injury persists, liver injury can lead to cirrhosis and liver failure and ultimately results in the development of liver cancer. Emerging evidence has indicated that long noncoding RNAs (lncRNAs) play an important role in the development of liver injury. However, the role of antisense Igf2r RNA (Airn) in acute liver injury and its underlying mechanism remain largely unclear. In this study, we show that Airn is upregulated in liver tissue and primary hepatocytes from an acute liver injury mouse model. Consistently, Airn is also overexpressed in serum samples of patients with acute-on-chronic liver failure and is negatively correlated with the Model for End-Stage Liver Disease (MELD) score. Moreover, gene knockout and rescue assays reveal that Airn alleviates CCl -induced liver injury by inhibiting hepatocyte apoptosis and oxidative stress . Further investigation reveals that Airn decreases H O -induced hepatocyte apoptosis . Mechanistically, we reveal that Airn represses CCl - and H O -induced enhancement of phosphorylation of p65 and IκBα, suggesting that Airn inhibits hepatocyte apoptosis by inactivating the NF-κB pathway. In conclusion, our results demonstrate that Airn can alleviate acute liver injury by inhibiting hepatocyte apoptosis via inactivating the NF-κB signaling pathway, and Airn could be a potential biomarker for acute liver injury.

Keywords

References

  1. Exp Ther Med. 2021 Apr;21(4):341 [PMID: 33732314]
  2. Int J Mol Sci. 2021 Jan 22;22(3): [PMID: 33499185]
  3. Front Pharmacol. 2020 Mar 31;11:388 [PMID: 32296336]
  4. Alcohol Alcohol. 2008 May-Jun;43(3):246-53 [PMID: 18263900]
  5. Molecules. 2019 Mar 20;24(6): [PMID: 30897831]
  6. Molecules. 2018 Feb 23;23(2): [PMID: 29473842]
  7. Arch Pharm Res. 2021 Apr;44(4):414-426 [PMID: 33759138]
  8. Oxid Med Cell Longev. 2020 Aug 19;2020:9329356 [PMID: 32922655]
  9. Science. 2008 Dec 12;322(5908):1717-20 [PMID: 18988810]
  10. Cell Death Dis. 2021 May 13;12(5):480 [PMID: 33986260]
  11. Cell. 2013 Jul 3;154(1):26-46 [PMID: 23827673]
  12. Hepatology. 1997 Jan;25(1):133-41 [PMID: 8985279]
  13. Acta Biochim Biophys Sin (Shanghai). 2020 Jun 20;52(6):665-674 [PMID: 32427312]
  14. Front Cell Dev Biol. 2020 Apr 08;8:242 [PMID: 32322582]
  15. Genomics. 2008 Dec;92(6):464-73 [PMID: 18789384]
  16. Clin Res Hepatol Gastroenterol. 2018 Feb;42(1):72-81 [PMID: 28601590]
  17. Crit Rev Toxicol. 2003;33(2):105-36 [PMID: 12708612]
  18. Chem Biodivers. 2020 Jan;17(1):e1900534 [PMID: 31730730]
  19. Lancet. 2019 Sep 7;394(10201):869-881 [PMID: 31498101]
  20. Evid Based Complement Alternat Med. 2017;2017:5140297 [PMID: 28246539]
  21. Evid Based Complement Alternat Med. 2017;2017:7953850 [PMID: 29250126]
  22. Int Immunopharmacol. 2019 Oct;75:105797 [PMID: 31421545]
  23. Gut. 2005 Jul;54(7):994-1002 [PMID: 15951548]
  24. Acta Biochim Biophys Sin (Shanghai). 2021 Apr 15;53(5):601-611 [PMID: 33783473]
  25. J Hepatol. 2000;32(1 Suppl):39-47 [PMID: 10728793]
  26. Circ Res. 2018 May 11;122(10):1347-1353 [PMID: 29483092]
  27. Vet Clin North Am Small Anim Pract. 2017 May;47(3):617-630 [PMID: 28065578]
  28. Cell Mol Immunol. 2016 May;13(3):301-15 [PMID: 26685902]
  29. Cell Death Dis. 2018 Nov 26;9(12):1164 [PMID: 30478280]
  30. Inflammation. 2021 Feb;44(1):194-205 [PMID: 32812145]
  31. Gene. 2020 Oct 20;758:144946 [PMID: 32649978]
  32. Am J Physiol Gastrointest Liver Physiol. 2007 Sep;293(3):G631-9 [PMID: 17640975]
  33. Nat Commun. 2017 Jul 26;8(1):144 [PMID: 28747678]
  34. Acta Biochim Biophys Sin (Shanghai). 2021 Mar 2;53(3):372-380 [PMID: 33511977]
  35. Exp Mol Pathol. 2020 Dec;117:104562 [PMID: 33129786]
  36. Biomed Pharmacother. 2019 Apr;112:108704 [PMID: 30818140]
  37. Gastroenterology. 2014 Oct;147(4):765-783.e4 [PMID: 25046161]
  38. Food Chem Toxicol. 2016 Jul;93:129-37 [PMID: 27137983]
  39. Metabolism. 2018 Apr;81:13-24 [PMID: 29106945]

MeSH Term

Animals
Mice
Apoptosis
End Stage Liver Disease
Hepatocytes
Liver
NF-kappa B
RNA, Long Noncoding
Severity of Illness Index
Signal Transduction

Chemicals

NF-kappa B
RNA, Long Noncoding
Air non-coding RNA, mouse

Word Cloud

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