Exploring Dysregulated Ferroptosis-Related Genes in Septic Myocardial Injury Based on Human Heart Transcriptomes: Evidence and New Insights.
database
ferroptosis
heart transcriptome
key genes
septic myocardial injury
Journal
Journal of inflammation research
ISSN: 1178-7031
Titre abrégé: J Inflamm Res
Pays: New Zealand
ID NLM: 101512684
Informations de publication
Date de publication:
2023
2023
Historique:
received:
07
12
2022
accepted:
25
02
2023
entrez:
16
3
2023
pubmed:
17
3
2023
medline:
17
3
2023
Statut:
epublish
Résumé
Sepsis is currently a common condition in emergency and intensive care units, and is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. Cardiac dysfunction caused by septic myocardial injury (SMI) is associated with adverse prognosis and has significant economic and human costs. The pathophysiological mechanisms underlying SMI have long been a subject of interest. Recent studies have identified ferroptosis, a form of programmed cell death associated with iron accumulation and lipid peroxidation, as a pathological factor in the development of SMI. However, the current understanding of how ferroptosis functions and regulates in SMI remains limited, particularly in the absence of direct evidence from human heart. We performed a sequential comprehensive bioinformatics analysis of human sepsis cardiac transcriptome data obtained through the GEO database. The lipopolysaccharide-induced mouse SMI model was used to validate the ferroptosis features and transcriptional expression of key genes. We identified widespread dysregulation of ferroptosis-related genes (FRGs) in SMI based on the human septic heart transcriptomes, deeply explored the underlying biological mechanisms and crosstalks, followed by the identification of key functional modules and hub genes through the construction of protein-protein interaction network. Eight key FRGs that regulate ferroptosis in SMI, including HIF1A, MAPK3, NOX4, PPARA, PTEN, RELA, STAT3 and TP53, were identified, as well as the ferroptosis features. All the key FRGs showed excellent diagnostic capability for SMI, part of them was associated with the prognosis of sepsis patients and the immune infiltration in the septic hearts, and potential ferroptosis-modulating drugs for SMI were predicted based on key FRGs. This study provides human septic heart transcriptome-based evidence and brings new insights into the role of ferroptosis in SMI, which is significant for expanding the understanding of the pathobiological mechanisms of SMI and exploring promising diagnostic and therapeutic targets for SMI.
Identifiants
pubmed: 36923465
doi: 10.2147/JIR.S400107
pii: 400107
pmc: PMC10010745
doi:
Types de publication
Journal Article
Langues
eng
Pagination
995-1015Informations de copyright
© 2023 Zou et al.
Déclaration de conflit d'intérêts
The authors report no conflicts of interest in this work.
Références
Aging Male. 2020 Sep;23(3):222-226
pubmed: 32183594
JAMA. 2018 Jan 2;319(1):62-75
pubmed: 29297082
Signal Transduct Target Ther. 2021 Feb 22;6(1):79
pubmed: 33612829
Front Immunol. 2017 Aug 24;8:1021
pubmed: 28970829
Semin Cancer Biol. 2020 Nov;66:89-100
pubmed: 30880243
Front Pharmacol. 2020 Mar 18;11:203
pubmed: 32256344
Biomolecules. 2021 Jul 10;11(7):
pubmed: 34356636
Redox Biol. 2020 Jan;28:101328
pubmed: 31574461
Biomed Pharmacother. 2022 Nov;155:113711
pubmed: 36126457
Am J Physiol Endocrinol Metab. 2022 Jul 1;323(1):E21-E32
pubmed: 35532075
Bioinformatics. 2015 Sep 15;31(18):3069-71
pubmed: 25990557
Neuron. 2019 Sep 25;103(6):1044-1055.e7
pubmed: 31473062
Biochem Biophys Res Commun. 2015 Dec 25;468(4):533-40
pubmed: 26518651
Nucleic Acids Res. 2021 Jan 8;49(D1):D1388-D1395
pubmed: 33151290
Cell Death Differ. 2020 Sep;27(9):2635-2650
pubmed: 32203170
Annu Rev Immunol. 2017 Apr 26;35:337-370
pubmed: 28142321
Front Immunol. 2022 Aug 05;13:956361
pubmed: 35990689
Biochim Biophys Acta Mol Basis Dis. 2019 Apr 1;1865(4):759-773
pubmed: 30342158
PLoS One. 2012;7(5):e36814
pubmed: 22590615
Cell Death Discov. 2022 Apr 9;8(1):187
pubmed: 35397620
Redox Biol. 2021 May;41:101947
pubmed: 33774476
Free Radic Biol Med. 2020 Nov 20;160:303-318
pubmed: 32846217
Biomed Res Int. 2021 Oct 22;2021:5669412
pubmed: 34722766
Autophagy. 2020 Aug;16(8):1482-1505
pubmed: 31679460
BMC Bioinformatics. 2013 Apr 15;14:128
pubmed: 23586463
JAMA. 2016 Feb 23;315(8):801-10
pubmed: 26903338
Nutr Rev. 2022 Sep 21;:
pubmed: 36130411
Nat Rev Cardiol. 2023 Jan;20(1):7-23
pubmed: 35788564
Curr Opin Crit Care. 2018 Aug;24(4):292-299
pubmed: 29846206
OMICS. 2012 May;16(5):284-7
pubmed: 22455463
Trends Endocrinol Metab. 2021 Jul;32(7):444-462
pubmed: 34006412
Mil Med Res. 2016 Sep 27;3:30
pubmed: 27708836
Cells. 2020 Jan 03;9(1):
pubmed: 31947892
PLoS One. 2013 Jul 22;8(7):e69452
pubmed: 23894482
Cell. 2021 Apr 1;184(7):1895-1913.e19
pubmed: 33657410
Cell Death Dis. 2020 Feb 3;11(2):86
pubmed: 32015337
Inflammation. 2020 Aug;43(4):1184-1200
pubmed: 32333359
Nat Rev Immunol. 2017 Jul;17(7):407-420
pubmed: 28436424
Nucleic Acids Res. 2021 Jan 8;49(D1):D437-D451
pubmed: 33211854
Pharmacol Res. 2010 May;61(5):410-8
pubmed: 20045729
Genome Biol. 2020 Jul 10;21(1):170
pubmed: 32650816
Circ Res. 2008 May 23;102(10):1239-46
pubmed: 18403730
Database (Oxford). 2020 Jan 1;2020:
pubmed: 32219413
Intensive Care Med. 2016 Dec;42(12):1958-1969
pubmed: 27695884
Front Pharmacol. 2019 Jan 21;9:1506
pubmed: 30719003
Front Cardiovasc Med. 2022 Aug 25;9:992653
pubmed: 36093172
Nat Rev Mol Cell Biol. 2021 Apr;22(4):266-282
pubmed: 33495651
EMBO Rep. 2022 Aug 3;23(8):e52280
pubmed: 35703725
Nature. 2021 Aug;596(7873):583-589
pubmed: 34265844
Drug Chem Toxicol. 2011 Apr;34(2):146-50
pubmed: 21314464
Front Cardiovasc Med. 2022 Aug 02;9:923066
pubmed: 35983185
Trends Cell Biol. 2016 Mar;26(3):165-176
pubmed: 26653790
N Engl J Med. 2022 Nov 17;387(20):1855-1864
pubmed: 36342163
J Infect Dis. 2016 Dec 1;214(11):1773-1783
pubmed: 27683819
Autophagy. 2021 Dec;17(12):4266-4285
pubmed: 33843441
J Intensive Care. 2020 Oct 01;8:76
pubmed: 33014378
J Biomed Sci. 2012 Aug 13;19(1):74
pubmed: 22889399
BMJ. 2016 May 23;353:i1585
pubmed: 27217054
Lancet. 2018 Jul 7;392(10141):75-87
pubmed: 29937192
Cell Prolif. 2022 Jan;55(1):e13158
pubmed: 34811833
Int Immunopharmacol. 2021 Jan;90:107160
pubmed: 33243604
Bioengineered. 2021 Dec;12(2):9367-9376
pubmed: 34787054
Circ Heart Fail. 2022 Jul;15(7):e008997
pubmed: 35730443
Bioengineered. 2021 Dec;12(2):9976-9990
pubmed: 34652258
Circulation. 2020 Aug 4;142(5):466-482
pubmed: 32403949
Exp Cell Res. 2021 Dec 15;409(2):112842
pubmed: 34563514
Proc Natl Acad Sci U S A. 2020 Dec 8;117(49):31189-31197
pubmed: 33229547
Med Sci Monit. 2019 Dec 06;25:9290-9298
pubmed: 31806860
Int J Mol Sci. 2019 Oct 29;20(21):
pubmed: 31671729
Sci Bull (Beijing). 2021 Nov 30;66(22):2257-2260
pubmed: 36654451
Clin Chem. 2000 May;46(5):650-7
pubmed: 10794747
Front Immunol. 2022 May 10;13:877634
pubmed: 35619718
Mol Med Rep. 2022 Nov;26(5):
pubmed: 36102305
Int J Mol Med. 2020 May;45(5):1477-1487
pubmed: 32323750
Blood. 2021 Aug 5;138(5):401-416
pubmed: 33895821
Chest. 2019 Feb;155(2):427-437
pubmed: 30171861
Crit Care. 2020 Jun 5;24(1):287
pubmed: 32503670
J Hazard Mater. 2022 Aug 15;436:129043
pubmed: 35525219
Biosci Rep. 2018 Apr 13;38(2):
pubmed: 29440462
Circ Res. 2022 Feb 4;130(3):418-431
pubmed: 35113662
Am J Physiol Heart Circ Physiol. 2016 Oct 1;311(4):H1051-H1062
pubmed: 27591219
Free Radic Biol Med. 2021 Mar;165:1-13
pubmed: 33486088
Redox Biol. 2019 Jun;24:101211
pubmed: 31108460
Nat Rev Cardiol. 2021 Jun;18(6):424-434
pubmed: 33473203
Crit Care. 2018 May 4;22(1):112
pubmed: 29724231
J Mol Cell Cardiol. 2016 Dec;101:11-24
pubmed: 27838370
Cell. 2022 Jul 7;185(14):2401-2421
pubmed: 35803244