TRDMT1 exhibited protective effects against LPS-induced inflammation in rats through TLR4-NF-κB/MAPK-TNF-α pathway.
Trdmt1
TLR4 pathway
TNF-α
inflammation
knockout rat
Journal
Animal models and experimental medicine
ISSN: 2576-2095
Titre abrégé: Animal Model Exp Med
Pays: United States
ID NLM: 101726292
Informations de publication
Date de publication:
04 2022
04 2022
Historique:
revised:
01
03
2022
received:
28
12
2021
accepted:
08
03
2022
pubmed:
28
4
2022
medline:
29
4
2022
entrez:
27
4
2022
Statut:
ppublish
Résumé
Inflammation is a complex physiological and pathological process. Although many types of inflammation are well characterized, their physiological functions are largely unknown. tRNA aspartic acid methyltransferase 1 (TRDMT1) has been implicated as a stress-related protein, but its intrinsic biological role is unclear. We constructed a Trdmt1 knockout rat and adopted the LPS-induced sepsis model. Survival curve, histopathological examination, expression of inflammatory factors, and protein level of TLR4 pathway were analyzed. Trdmt1 deletion had no obvious impact on development and growth. Trdmt1 deletion slightly increased the mortality during aging. Our data showed that Trdmt1 strongly responded in LPS-treated rats, and Trdmt1 knockout rats were vulnerable to LPS treatment with declined survival rate. We also observed more aggravated tissue damage and more cumulative functional cell degeneration in LPS-treated knockout rats compared with control rats. Further studies showed upregulated TNF-α level in liver, spleen, lung, and serum tissues, which may be explained by enhanced p65 and p38 phosphorylation. Our data demonstrated that Trdmt1 plays a protective role in inflammation by regulating the TLR4-NF-κB/MAPK-TNF-α pathway. This work provides useful information to understand the TRDMT1 function in inflammation.
Sections du résumé
BACKGROUND
Inflammation is a complex physiological and pathological process. Although many types of inflammation are well characterized, their physiological functions are largely unknown. tRNA aspartic acid methyltransferase 1 (TRDMT1) has been implicated as a stress-related protein, but its intrinsic biological role is unclear.
METHODS
We constructed a Trdmt1 knockout rat and adopted the LPS-induced sepsis model. Survival curve, histopathological examination, expression of inflammatory factors, and protein level of TLR4 pathway were analyzed.
RESULTS
Trdmt1 deletion had no obvious impact on development and growth. Trdmt1 deletion slightly increased the mortality during aging. Our data showed that Trdmt1 strongly responded in LPS-treated rats, and Trdmt1 knockout rats were vulnerable to LPS treatment with declined survival rate. We also observed more aggravated tissue damage and more cumulative functional cell degeneration in LPS-treated knockout rats compared with control rats. Further studies showed upregulated TNF-α level in liver, spleen, lung, and serum tissues, which may be explained by enhanced p65 and p38 phosphorylation.
CONCLUSIONS
Our data demonstrated that Trdmt1 plays a protective role in inflammation by regulating the TLR4-NF-κB/MAPK-TNF-α pathway. This work provides useful information to understand the TRDMT1 function in inflammation.
Identifiants
pubmed: 35474613
doi: 10.1002/ame2.12221
pmc: PMC9043724
doi:
Substances chimiques
Lipopolysaccharides
0
NF-kappa B
0
Tlr4 protein, rat
0
Toll-Like Receptor 4
0
Tumor Necrosis Factor-alpha
0
DNA (Cytosine-5-)-Methyltransferases
EC 2.1.1.37
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
172-182Informations de copyright
© 2022 The Authors. Animal Models and Experimental Medicine published by John Wiley & Sons Australia, Ltd on behalf of The Chinese Association for Laboratory Animal Sciences.
Références
J Clin Invest. 2017 Nov 1;127(11):4124-4135
pubmed: 28990935
Animal Model Exp Med. 2020 Aug 10;3(3):215-228
pubmed: 33024943
Cell Rep. 2013 Sep 12;4(5):931-7
pubmed: 24012760
Proc Natl Acad Sci U S A. 2006 Feb 14;103(7):2274-9
pubmed: 16461893
Cell Mol Life Sci. 2021 Feb;78(4):1233-1261
pubmed: 33057840
J Biol Chem. 2005 Jan 14;280(2):861-4
pubmed: 15533947
Chem Biol Interact. 2014 Sep 5;220:51-63
pubmed: 24928743
Int Immunopharmacol. 2020 Dec;89(Pt B):107087
pubmed: 33075714
JAMA. 2011 Dec 21;306(23):2594-605
pubmed: 22187279
Nat Commun. 2018 Mar 21;9(1):1163
pubmed: 29563491
Methods Mol Biol. 2017;1642:37-52
pubmed: 28815492
Hypertension. 2012 Jul;60(1):81-9
pubmed: 22665122
Exp Gerontol. 2018 May;105:10-18
pubmed: 29275161
Nat Struct Mol Biol. 2012 Sep;19(9):900-5
pubmed: 22885326
J Cell Physiol. 2017 Dec;232(12):3714-3726
pubmed: 28177119
Front Cell Dev Biol. 2021 Sep 23;9:700661
pubmed: 34631699
Transplantation. 2020 Apr;104(4):715-723
pubmed: 31764762
Intensive Care Med. 2009 May;35(5):871-81
pubmed: 19066848
Cancer J. 2017 Jul/Aug;23(4):201-205
pubmed: 28731941
Cell. 2010 Mar 19;140(6):805-20
pubmed: 20303872
Vaccines (Basel). 2017 Oct 04;5(4):
pubmed: 28976923
RNA Biol. 2016 Jul 2;13(7):605-12
pubmed: 27163284
Nat Rev Nephrol. 2018 Jul;14(7):417-427
pubmed: 29691495
Nat Cell Biol. 2018 May;20(5):535-540
pubmed: 29695786
Biochim Biophys Acta Mol Basis Dis. 2017 Oct;1863(10 Pt B):2564-2573
pubmed: 28115287
RNA Biol. 2021 Dec;18(12):2531-2545
pubmed: 34110975
Animal Model Exp Med. 2021 May 03;4(3):249-260
pubmed: 34557651
EMBO J. 2015 Sep 14;34(18):2350-62
pubmed: 26271101
Biochem J. 2017 Jun 6;474(12):2009-2026
pubmed: 28476776
Cytokine. 2008 May;42(2):145-151
pubmed: 18304834
Epigenetics. 2011 Jan;6(1):103-13
pubmed: 20864816
Aging (Albany NY). 2021 Jun 17;13(12):15833-15874
pubmed: 34139673
Int J Mol Sci. 2020 Oct 31;21(21):
pubmed: 33142933
Animal Model Exp Med. 2019 Mar 12;2(1):18-24
pubmed: 31016283
Redox Biol. 2018 Apr;14:20-34
pubmed: 28843151
Animal Model Exp Med. 2020 Aug 07;3(3):237-244
pubmed: 33024945
Cells. 2020 Jul 22;9(8):
pubmed: 32708015
Adv Clin Exp Med. 2018 Apr;27(4):547-551
pubmed: 29558045
Proc Natl Acad Sci U S A. 2013 May 21;110(21):8627-31
pubmed: 23641003
Genes Dev. 2010 Aug 1;24(15):1590-5
pubmed: 20679393
Adv Nutr. 2015 May 15;6(3):293S-301S
pubmed: 25979502
Trends Immunol. 2013 Mar;34(3):129-36
pubmed: 23036432
PLoS One. 2014 Mar 05;9(3):e89413
pubmed: 24598943
Mol Biochem Parasitol. 2006 May;147(1):48-54
pubmed: 16497397
Animal Model Exp Med. 2022 Apr;5(2):172-182
pubmed: 35474613
Trends Immunol. 2005 Sep;26(9):469-76
pubmed: 16006187
Nucleic Acids Res. 1995 Jan 25;23(2):203-10
pubmed: 7862522
PLoS One. 2016 Jun 06;11(6):e0156953
pubmed: 27270731
Int J Mol Sci. 2019 Oct 29;20(21):
pubmed: 31671729
Nat Rev Genet. 2018 Feb;19(2):81-92
pubmed: 29033456
Front Plant Sci. 2020 Aug 05;11:1185
pubmed: 32849734
Science. 2006 Jan 20;311(5759):395-8
pubmed: 16424344
Genes Dev. 2007 Feb 1;21(3):261-6
pubmed: 17289917
Mol Med Rep. 2020 Feb;21(2):959-968
pubmed: 31974603
Front Genet. 2021 Apr 20;12:615491
pubmed: 33959146
Immunobiology. 2019 Jan;224(1):172-176
pubmed: 30342883
Cell Mol Life Sci. 2015 Feb;72(3):557-581
pubmed: 25332099
J Ovarian Res. 2020 Feb 3;13(1):12
pubmed: 32014030