Top

European Journal of Medical Research

Published in:

Open Access 01-12-2023 | Septicemia | Research

LncRNA–mRNA expression profile and functional network of vascular dysfunction in septic rats

Authors: Ye-Chen Han, Zhu-Jun Shen, Yi-Ning Wang, Ruo-Lan Xiang, Hong-Zhi Xie

Published in: European Journal of Medical Research | Issue 1/2023

Abstract

Background

We used microarrays to analyse the changes in long non-coding RNAs (lncRNAs) and mRNAs in aorta tissue in model rats with lipopolysaccharide-induced sepsis and determined the lncRNA–mRNA and lncRNA–miRNA–mRNA functional networks.

Methods

Wistar rats were intraperitoneally injected with lipopolysaccharide, and the lncRNA and mRNA expression profiles in the aorta were evaluated using microarrays. The functions of the differentially expressed mRNAs were analysed using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses. We then constructed coding/non-coding co-expression and competing endogenous RNA networks to study the mechanisms related to sepsis in rats.

Results

We identified 503 differentially expressed lncRNAs and 2479 differentially expressed mRNAs in the model rats with lipopolysaccharide-induced sepsis. Mitochondrial fission process 1 (MTFP1) was the most significantly down-regulated mRNA. Bioinformatics analysis showed that the significantly down-regulated mRNAs in the sepsis models were in pathways related to mitochondrial structure, function, and energy metabolism. Coding/non-coding co-expression and competing endogenous RNA analyses were conducted using 12 validated lncRNAs in combination with all mRNAs. The coding/non-coding co-expression analysis showed that the 12 validated lncRNAs were mainly regulatory factors for abnormal energy metabolism, including mitochondrial structure damage and aberrant mitochondrial dynamics. The competing endogenous RNA analysis revealed that the potential functions of these 12 lncRNAs might be related to the inflammatory response.

Conclusion

We determined the differentially expressed lncRNAs and mRNAs in the aorta of septic rats using microarrays. Further studies on these lncRNAs will help elucidate the mechanism of sepsis at the genetic level and may identify potential therapeutic targets.

Available only for authorised users

Huang M, Cai S, Su J. The pathogenesis of sepsis and potential therapeutic targets. Int J Mol Sci. 2019;20(21):5376. https://doi.org/10.3390/ijms20215376.CrossRef

Singer M, Deutschman CS, Seymour CW, Shankar-Hari M, Annane D, Bauer M, et al. The third international consensus definitions for sepsis and septic shock (Sepsis-3). JAMA. 2016;315(8):801–10. https://doi.org/10.1001/jama.2016.0287.CrossRef

Liu X, Liu R, Dai Z, Wu H, Lin M, Tian F, et al. Effect of Shenfu injection on lipopolysaccharide (LPS)-induced septic shock in rabbits. J Ethnopharmacol. 2019;234:36–43. https://doi.org/10.1016/j.jep.2019.01.008.CrossRef

Abdulmahdi W, Patel D, Rabadi MM, Azar T, Jules E, Lipphardt M, et al. HMGB1 redox during sepsis. Redox Biol. 2017;13:600–7. https://doi.org/10.1016/j.redox.2017.08.001.CrossRef

Bikfalvi A. History and conceptual developments in vascular biology and angiogenesis research: a personal view. Angiogenesis. 2017;20(4):463–78. https://doi.org/10.1007/s10456-017-9569-2.CrossRef

Fleischmann C, Scherag A, Adhikari NK, Hartog CS, Tsaganos T, Schlattmann P, et al. Assessment of global incidence and mortality of hospital-treated sepsis. Current estimates and limitations. Am J Respir Crit Care Med. 2016;193(3):259–72. https://doi.org/10.1164/rccm.201504-0781OC.CrossRef

Stanzani G, Duchen MR, Singer M. The role of mitochondria in sepsis-induced cardiomyopathy. Biochim Biophys Acta Mol Basis Dis. 2019;1865(4):759–73. https://doi.org/10.1016/j.bbadis.2018.10.011.CrossRef

Dykes IM, Emanueli C. Transcriptional and post-transcriptional gene regulation by long non-coding RNA. Genom Proteom Bioinform. 2017;15(3):177–86. https://doi.org/10.1016/j.gpb.2016.12.005.CrossRef

Quinn JJ, Chang HY. Unique features of long non-coding RNA biogenesis and function. Nat Rev Genet. 2016;17(1):47–62. https://doi.org/10.1038/nrg.2015.10.CrossRef

10.

Sun F, Zhuang Y, Zhu H, Wu H, Li D, Zhan L, et al. LncRNA PCFL promotes cardiac fibrosis via miR-378/GRB2 pathway following myocardial infarction. J Mol Cell Cardiol. 2019;133:188–98. https://doi.org/10.1016/j.yjmcc.2019.06.011.CrossRef

11.

Fan Y, Sheng W, Meng Y, Cao Y, Li R. LncRNA PTENP1 inhibits cervical cancer progression by suppressing miR-106b. Artif Cells Nanomed Biotechnol. 2020;48(1):393–407. https://doi.org/10.1080/21691401.2019.1709852.CrossRef

12.

Fang Y, Hu J, Wang Z, Zong H, Zhang L, Zhang R, et al. LncRNA H19 functions as an Aquaporin 1 competitive endogenous RNA to regulate microRNA-874 expression in LPS sepsis. Biomed Pharmacother. 2018;105:1183–91. https://doi.org/10.1016/j.biopha.2018.06.007.CrossRef

13.

Zhang CC, Niu F. LncRNA NEAT1 promotes inflammatory response in sepsis-induced liver injury via the Let-7a/TLR4 axis. Int Immunopharmacol. 2019;75:105731. https://doi.org/10.1016/j.intimp.2019.105731.CrossRef

14.

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/NFkappaB. Int Immunopharmacol. 2018;55:69–76. https://doi.org/10.1016/j.intimp.2017.11.038.CrossRef

15.

Zhang TN, Yang N, Goodwin JE, Mahrer K, Li D, Xia J, et al. Characterization of circular RNA and microRNA profiles in septic myocardial depression: a lipopolysaccharide-induced rat septic shock model. Inflammation. 2019;42(6):1990–2002. https://doi.org/10.1007/s10753-019-01060-8.CrossRef

16.

Liu X, Xu Q, Mei L, Lei H, Wen Q, Miao J, et al. Paeonol attenuates acute lung injury by inhibiting HMGB1 in lipopolysaccharide-induced shock rats. Int Immunopharmacol. 2018;61:169–77. https://doi.org/10.1016/j.intimp.2018.05.032.CrossRef

17.

Song Y, Wang X, Hou A, Li H, Lou J, Liu Y, et al. Integrative analysis of lncRNA and mRNA and profiles in postoperative delirium patients. Front Aging Neurosci. 2021;13:665935. https://doi.org/10.3389/fnagi.2021.665935.CrossRef

18.

Nie MW, Han YC, Shen ZJ, Xie HZ. Identification of circRNA and mRNA expression profiles and functional networks of vascular tissue in lipopolysaccharide-induced sepsis. J Cell Mol Med. 2020;24(14):7915–27. https://doi.org/10.1111/jcmm.15424.CrossRef

19.

Fink MP. Animal models of sepsis. Virulence. 2014;5(1):143–53. https://doi.org/10.4161/viru.26083.CrossRef

20.

Yang N, Shi XL, Zhang BL, Rong J, Zhang TN, Xu W, et al. The Trend of β3-adrenergic receptor in the development of septic myocardial depression: a lipopolysaccharide-induced rat septic shock model. Cardiology. 2018;139(4):234–44. https://doi.org/10.1159/000487126.CrossRef

21.

Xiao T, Sun J, Xing Z, Xie F, Yang L, Ding W. MTFP1 overexpression promotes the growth of oral squamous cell carcinoma by inducing ROS production. Cell Biol Int. 2020;44(3):821–9. https://doi.org/10.1002/cbin.11278.CrossRef

22.

Liu MY, Jin J, Li SL, Yan J, Zhen CL, Gao JL, et al. Mitochondrial fission of smooth muscle cells is involved in artery constriction. Hypertension. 2016;68(5):1245–54. https://doi.org/10.1161/hypertensionaha.116.07974.CrossRef

23.

Mishra P, Chan DC. Metabolic regulation of mitochondrial dynamics. J Cell Biol. 2016;212(4):379–87. https://doi.org/10.1083/jcb.201511036.CrossRef

24.

Dikalova AE, Pandey A, Xiao L, Arslanbaeva L, Sidorova T, Lopez MG, et al. Mitochondrial deacetylase Sirt3 reduces vascular dysfunction and hypertension while Sirt3 depletion in essential hypertension is linked to vascular inflammation and oxidative stress. Circ Res. 2020;126(4):439–52. https://doi.org/10.1161/circresaha.119.315767.CrossRef

25.

Lado-Abeal J, Martinez-Sanchez N, Cocho JA, Martin-Pastor M, Castro-Piedras I, Couce-Pico ML, et al. Lipopolysaccharide (LPS)-induced septic shock causes profound changes in myocardial energy metabolites in pigs. Metabolomics. 2018;14(10):131. https://doi.org/10.1007/s11306-018-1433-x.CrossRef

26.

Maestraggi Q, Lebas B, Clere-Jehl R, Ludes PO, Chamaraux-Tran TN, Schneider F, et al. Skeletal muscle and lymphocyte mitochondrial dysfunctions in septic shock trigger ICU-acquired weakness and sepsis-induced immunoparalysis. Biomed Res Int. 2017;2017:7897325. https://doi.org/10.1155/2017/7897325.CrossRef

27.

Cao Y, Ma W, Liu Z, Pei Y, Zhu Y, Chen F, et al. Early predictive value of platelet function for clinical outcome in sepsis. J Infect. 2022;84(5):628–36. https://doi.org/10.1016/j.jinf.2022.02.004.CrossRef

28.

Shang X, Li J, Yu R, Zhu P, Zhang Y, Xu J, et al. Sepsis-related myocardial injury is associated with Mst1 upregulation, mitochondrial dysfunction and the Drp1/F-actin signaling pathway. J Mol Histol. 2019;50(2):91–103. https://doi.org/10.1007/s10735-018-09809-5.CrossRef

29.

Armartmuntree N, Murata M, Techasen A, Yongvanit P, Loilome W, Namwat N, et al. Prolonged oxidative stress down-regulates Early B cell factor 1 with inhibition of its tumor suppressive function against cholangiocarcinoma genesis. Redox Biol. 2018;14:637–44. https://doi.org/10.1016/j.redox.2017.11.011.CrossRef

30.

Areti A, Komirishetty P, Akuthota M, Malik RA, Kumar A. Melatonin prevents mitochondrial dysfunction and promotes neuroprotection by inducing autophagy during oxaliplatin-evoked peripheral neuropathy. J Pineal Res. 2017. https://doi.org/10.1111/jpi.12393.CrossRef

31.

Lelubre C, Vincent JL. Mechanisms and treatment of organ failure in sepsis. Nat Rev Nephrol. 2018;14(7):417–27. https://doi.org/10.1038/s41581-018-0005-7.CrossRef

32.

Hou Y, Wang XF, Lang ZQ, Jin YC, Fu JR, Xv XM, et al. Adiponectin is protective against endoplasmic reticulum stress-induced apoptosis of endothelial cells in sepsis. Braz J Med Biol Res. 2018;51(12):e7747. https://doi.org/10.1590/1414-431x20187747.CrossRef

Title: LncRNA–mRNA expression profile and functional network of vascular dysfunction in septic rats
Authors: Ye-Chen Han
Zhu-Jun Shen
Yi-Ning Wang
Ruo-Lan Xiang
Hong-Zhi Xie
Publication date: 01-12-2023
Publisher: BioMed Central
Keywords: Septicemia
Septicemia
Published in: European Journal of Medical Research / Issue 1/2023
Electronic ISSN: 2047-783X
DOI: https://doi.org/10.1186/s40001-022-00961-z

Keynote webinar | Spotlight on medication adherence

Springer Medicine

LncRNA–mRNA expression profile and functional network of vascular dysfunction in septic rats

Abstract

Background

Methods

Results

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusion

Please log in to get access to this content

Other articles of this Issue 1/2023

Dynamic change of the systemic immune inflammation index is a risk factor for patients with oropharyngeal cancer: a case control study and an additional HPV-status subgroup analysis

Photodistributed Stevens–Johnson syndrome and toxic epidermal necrolysis: a systematic review and proposal for a new diagnostic classification

Accuracy of the estimations of respiratory mechanics using an expiratory time constant in passive and active breathing conditions: a bench study

Common clinical blood and urine biomarkers for ischemic stroke: an Estonian Electronic Health Records database study

Identification of a potential bioinformatics-based biomarker in keloids and its correlation with immune infiltration

The role of cortisol in immunosuppression in subarachnoid haemorrhage