Issue

Vol. 66 No. 5: Issue 5

The undersigned hereby assign all rights, included but not limited to copyright, for this manuscript to CMB Association upon its submission for consideration to publication on Cellular and Molecular Biology. The rights assigned include, but are not limited to, the sole and exclusive rights to license, sell, subsequently assign, derive, distribute, display and reproduce this manuscript, in whole or in part, in any format, electronic or otherwise, including those in existence at the time this agreement was signed. The authors hereby warrant that they have not granted or assigned, and shall not grant or assign, the aforementioned rights to any other person, firm, organization, or other entity. All rights are automatically restored to authors if this manuscript is not accepted for publication.

LncRNA MEG3 expression in sepsis and its effect on LPS-induced macrophage function

https://doi.org/10.14715/cmb/2020.66.5.23
Xinrong Pan
Department of Infectious Disease, Shengzhou People's Hospital(The First Affiliated Hospital of Zhejiang University Shengzhou Branch), Shengzhou, 312400, China
Lingling He
Zhuji People's Hospital, Zhuji, 311800, China

Corresponding Author(s) : Lingling He

382665095@qq.com

Cellular and Molecular Biology, Vol. 66 No. 5: Issue 5

Abstract

Sepsis is a dangerous disease that is caused by an overreaction of the body's immune system to infection and gradually spreads throughout the body. This experiment was carried out to explore the expression of LncRNA MEG3 in sepsis and its effect on LPS-induced macrophage function. Methods 60 sepsis patients admitted to our hospital from February 2017 to September 2018 were selected as the sepsis group, and 50 non-septic patients diagnosed and treated in our hospital during the same period were selected as the control group. qRT-PCR was used to detect the expression level of MEG3. ROC curve was used to analyze the diagnostic value of serum MEG3 in sepsis. The human macrophage cell line U937 was cultured in vitro and randomly divided into NC group, LPS group, LPS + pcDNA group, and LPS + pcDNA-MEG3 group. Flow cytometry was applied to detect the apoptosis rate. The levels of IL-1β and TNF-α were detected by ELISA. Western blot was used to detect the expression of Bax, Bcl-2 and NF-κB signaling pathway-related proteins p65 and p-p65. Results: The expression level of serum MEG3 in the sepsis group was significantly lower than that in the control group (P <0.05). ROC curve analysis showed that the AUC area was 0.856, the sensitivity was 0.700, and the specificity was 0.883. Compared with the NC group, the macrophage apoptosis rate in the LPS group was increased (P <0.05), the levels of Bax and p-p65 protein were significantly increased (P <0.05), and the level of Bcl-2 protein was decreased (P <0.05), the levels of IL-1β and TNF-α were increased (P <0.05). Compared with the LPS + pcDNA group, the apoptosis rate of the LPS + pcDNA-MEG3 group was significantly reduced (P <0.05), the levels of Bax and p-p65 protein were reduced (P <0.05), and the level of Bcl-2 protein was significantly increased (P <0.05), the levels of IL-1β and TNF-α were reduced (P <0.05). Conclusion: The low expression of LncRNA MEG3 in the serum of patients with sepsis can predict the occurrence of sepsis. Overexpression of MEG3 can inhibit LPS-induced macrophage apoptosis and secretion of inflammatory factors by inhibiting the activation of the NF-κB signaling pathway.

Keywords

LncRNA MEG3 sepsis lipopolysaccharide macrophage apoptosis inflammatory factor
Pan, X., & He, L. (2020). LncRNA MEG3 expression in sepsis and its effect on LPS-induced macrophage function. Cellular and Molecular Biology, 66(5), 131–136. https://doi.org/10.14715/cmb/2020.66.5.23
Download Citation
Endnote/Zotero/Mendeley (RIS)
BibTeX
References
  1. Reference
  2. Shangxun Z, Junjie L, Wei Z, Yutong W, Wenyuan J, Shanshou L, Yanjun W, Qianmei W, Zhusheng F, Chaoping Y, Ran Z. ADAR1 Alleviates Inflammation in a Murine Sepsis Model via the ADAR1-miR-30a-SOCS3 Axis. Mediators Inflamm 2020.
  3. Kim JY, Joo YS, Lee S, Lee JY, Park JT, Han SH, Yoo TH, Kang SW. Septicemia, necrotizing fasciitis, and peritonitis due to Vibrio vulnificus treated with early use of polymyxin B hemoperfusion in a patient undergoing CAPD: a case report. BMC Nephrol 2020; 21(1):1-6.
  4. Bhalala US. Predictors of outcomes of severe sepsis in children in the Indian subcontinent - What's the big picture. J Postgrad Med 2020; 66(2): 63-64.
  5. Wooldridge G, Murthy S, Kissoon N. Core outcome set in paediatric sepsis in low- and middle-income countries: a study protocol. BMJ Open 2020; 10(4): e034960-e034970.
  6. Hung YL, Fang SH, Wang SC, Cheng WC, Liu PL, Su CC, Chen CS, Huang MY, Hua KF, Shen KH, Wang YT. Corylin protects LPS-induced sepsis and attenuates LPS-induced inflammatory response. Sci Rep 2017; 7:46299.
  7. Chen H, Wang X, Yan X, Cheng X, He X, Zheng W. LncRNA MALAT1 regulates sepsis-induced cardiac inflammation and dysfunction via interaction with miR-125b and p38 MAPK/NFκB. Int Immunopharmacol 2018; 55:69-76.
  8. Obaid M, Udden SN, Deb P, Shihabeddin N, Zaki MH, Mandal SS. LncRNA HOTAIR regulates lipopolysaccharide-induced cytokine expression and inflammatory response in macrophages. Sci Rep 2018; 8(1):1-8.
  9. Li G, Liu Y, Meng F, Xia Z, Wu X, Fang Y, Zhang C, Zhang Y, Liu D. LncRNA MEG3 inhibits rheumatoid arthritis through miR"141 and inactivation of AKT/mTOR signalling pathway. J Cell Mol Med 2019; 23(10):7116-20.
  10. Li X, Zhang Q, Yang Z. Silence of MEG3 intensifies lipopolysaccharide-stimulated damage of human lung cells through modulating miR-4262. Artif Cells Nanomed Biotechnol 2019; 47(1): 2369-2378.
  11. Wang Z, Chi X, Liu L, Wang Y, Mei X, Yang Y, Jia T. Long noncoding RNA maternally expressed gene 3 knockdown alleviates lipopolysaccharide-induced inflammatory injury by up-regulation of miR-203 in ATDC5 cells. Biomed Pharmacother 2018; 100:240-9.
  12. Tessaro FH, Ayala TS, Nolasco EL, Bella LM, Martins JO. Insulin influences LPS-Induced TNF-α and IL-6 release through distinct pathways in mouse macrophages from different compartments. Cell Physiol Biochem 2017; 42(5):2093-104.
  13. Lou Y, Huang Z. microRNA-15a-5p participates in sepsis by regulating the inflammatory response of macrophages and targeting TNIP2. Exp Ther Med 2020; 19(4): 3060-3068.
  14. Jin K, Ma Y, Manrique"Caballero CL, Li H, Emlet DR, Li S, Baty CJ, Wen X, Kim"Campbell N, Frank A, Menchikova EV. Activation of AMP"activated protein kinase during sepsis/inflammation improves survival by preserving cellular metabolic fitness. FASEB J 2020; 34(5):7036-57.
  15. Wang HR, Guo XY, Liu XY, Song X. Down-regulation of lncRNA CASC9 aggravates sepsis-induced acute lung injury by regulating miR-195-5p/PDK4 axis. Inflamm Res 2020.
  16. Li Y, Song J, Xie Z, Liu M, Sun K. Long noncoding RNA colorectal neoplasia differentially expressed alleviates sepsis"induced liver injury via regulating miR"126"5p. IUBMB Life 2020; 72(3):440-51.
  17. Tong P, Peng QH, Gu LM, Xie WW, Li WJ. LncRNA-MEG3 alleviates high glucose induced inflammation and apoptosis of retina epithelial cells via regulating miR-34a/SIRT1 axis. Exp Mol Pathol 2019; 107:102-9.
  18. Li Y, Zhang S, Zhang C, Wang M. LncRNA MEG3 inhibits the inflammatory response of ankylosing spondylitis by targeting miR-146a. Mol Cell Biochem 2020; 1-8.
  19. Liang J, Wang Q, Li JQ, Guo T, Yu D. Long non-coding RNA MEG3 promotes cerebral ischemia-reperfusion injury through increasing pyroptosis by targeting miR-485/AIM2 axis. Exp Neurol 2020; 325:113139.
  20. Song B, Ye L, Wu S, Jing Z. Long non-coding RNA MEG3 regulates CSE-induced apoptosis and inflammation via regulating miR-218 in 16HBE cells. Biochem Biophys Res Commun 2020; 521(2):368-74.
  21. Chen MJ, Wang XG, Sun ZX, Liu XC. Diagnostic value of LncRNA-MEG3 as a serum biomarker in patients with hepatitis B complicated with liver fibrosis. Eur Rev Med Pharmacol Sci 2019; 23(10):4360-7.
  22. Yan L, Liu Z, Yin H, Guo Z, Luo Q. Silencing of MEG3 inhibited ox"LDL"induced inflammation and apoptosis in macrophages via modulation of the MEG3/miR"204/CDKN2A regulatory axis. Cell Biol Int 2019; 43(4):409-20.
  23. Nadeem A, Alharbi NO, Vliagoftis H, Tyagi M, Ahmad SF, Sayed"Ahmed MM. Proteinase activated receptor"2"mediated dual oxidase"2 up"regulation is involved in enhanced airway reactivity and inflammation in a mouse model of allergic asthma. Immunol 2015; 145(3):391-403.
  24. Jia Y, He W, Zhang H, He L, Wang Y, Zhang T, Peng J, Sun P, Qian Y. Morusin Ameliorates IL-1β-Induced Chondrocyte Inflammation and Osteoarthritis via NF-κB Signal Pathway. Drug Design, Dev Ther 2020; 14:1227.
  25. Ji Y, Fang QY, Wang SN, Zhang ZW, Hou ZJ, Li JN, Fu SQ. Lnc-RNA BLACAT1 regulates differentiation of bone marrow stromal stem cells by targeting miR-142-5p in osteoarthritis. Eur Rev Med Pharmacol Sci 2020; 24(6):2893-901.
  26. Ding SL, Pang ZY, Chen XM, Li Z, Liu XX, Zhai QL, Huang JM, Ruan ZY. Urolithin a attenuates IL-1β-induced inflammatory responses and cartilage degradation via inhibiting the MAPK/NF-κB signaling pathways in rat articular chondrocytes. J Inflamm 2020; 17(1):1-3.
  27. Song S, Pan Y, Li H, Zhen H. MiR-1202 Exerts Neuroprotective Effects on OGD/R Induced Inflammation in HM Cell by Negatively Regulating Rab1a Involved in TLR4/NF-κB Signaling Pathway. Neurochem Res 2020; 1-0.
  28. Yang C, Yang W, He Z, He H, Yang X, Lu Y, Li H. Kaempferol Improves Lung Ischemia-Reperfusion Injury via Antiinflammation and Antioxidative Stress Regulated by SIRT1/HMGB1/NF-κB Axis. Front Pharmacol 2020; 10:1635.
  29. Wang F, Han Y, Xi S, Lu Y. Catechins reduce inflammation in lipopolysaccharide"stimulated dental pulp cells by inhibiting activation of the NF"κB pathway. Oral Dis 2020; 26(4):815-21.
  30. Hu F, Jiang J, Yu G, Zang H, Sun H. Propofol Pretreatment Prevents Oxygen-Glucose Deprivation/Reoxygenation (OGD/R)-induced Inflammation Through Nuclear Transcription Factor ΚB (NF-ΚB) Pathway in Neuroblastoma Cells. Curr Neurovasc Res 2020; 17(1):27-34.
  31. Hatipoglu OF, Yaykasli KO, Dogan M, Yaykasli E, Bender O, Yasar T, Tapan S, Gunduz M. NF-κB and MAPKs are involved in resistin caused ADAMTS-5 induction in Human Chondrocytes. Clin Invest Med 2015; 38(4): E248-E254.
  32. Yaykasli KO. Visfatin promotes a disintegrin and metalloproteinase with thrombospondin motifs-5 gene expression through p38 MAPK and NF-kappa B pathways in human chondrocytes, FEBS J 2016; 283:50–50.
  33. Liu J, Guo S, Jiang K, Zhang T, Zhiming W, Yaping Y, Jing Y, Shaukat A, Deng G. miR"488 mediates negative regulation of the AKT/NF"κB pathway by targeting Rac1 in LPS"induced inflammation. J Cell Physiol 2020; 235(5):4766-77.
  34. Azimi-Nezhad M. Vascular endothelial growth factor from embryonic status to cardiovascular pathology. Rep Biochem Mol Biol 2014;2(2):59"69.
  35. Bordbar M, Darvishzadeh R, Pazhouhandeh M, Kahrizi D. An overview of genome editing methods based on endonucleases. Modern Genetics J 2020; 15(2): 75-92.
Read More
Author biographies is not available.
Crossref
Scopus
Google Scholar
Europe PMC
Download this PDF file
PDF
Statistic
Read Counter : 902 Download : 507