NOS2/miR-493-5p Signaling Regulates in the LPS-Induced Inflammatory Response in the RAW264.7 Cells.

Szczegóły
Abstrakt

Tytuł:: NOS2/miR-493-5p Signaling Regulates in the LPS-Induced Inflammatory Response in the RAW264.7 Cells.
Autorzy:: Li X; Clinical Laboratory, The Third People's Hospital of Kunming, Kunming, China.
Yang Y; Department of Hepatology, The Third People's Hospital of Kunming, Kunming, China.
Lu N; Department of Respiratory Medicine, The Third People's Hospital of Kunming, Kunming, China.
Luo F; Clinical Laboratory, The Third People's Hospital of Kunming, Kunming, China.
Fan R; School of Public Health, Dali University, Dali, China.
Peng N; School of Life Science and Technology and School of Mechanical Engineering, Xi'an Jiaotong University, Xi'an, 710049, China. .
Źródło:: Biochemical genetics [Biochem Genet] 2023 Jun; Vol. 61 (3), pp. 1097-1112. Date of Electronic Publication: 2022 Nov 30.
Typ publikacji:: Journal Article
Język:: English
Imprint Name(s):: Publication: 1999- : New York : Kluwer Academic/Plenum Publishers
Original Publication: New York, Plenum Press.
MeSH Terms:: MicroRNAs*/genetics
MicroRNAs*/metabolism
Tuberculosis*/metabolism
Animals ; Mice ; Cytokines/metabolism ; Inflammation/metabolism ; Inflammation/microbiology ; Lipopolysaccharides/pharmacology ; Nitric Oxide Synthase Type II/genetics ; Nitric Oxide Synthase Type II/metabolism ; Signal Transduction
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Contributed Indexing:: Keywords: Bioinformatics; Lipopolysaccharides; NOS2; RAW264.7 cells; Tuberculosis; miR-493-5p
Substance Nomenclature:: 0 (Cytokines)
0 (Lipopolysaccharides)
0 (MicroRNAs)
EC 1.14.13.39 (Nitric Oxide Synthase Type II)
0 (MIRN493 microRNA, mouse)
Entry Date(s):: Date Created: 20221130 Date Completed: 20240122 Latest Revision: 20240122
Update Code:: 20240122
DOI:: 10.1007/s10528-022-10297-2
PMID:: 36449151
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Tuberculosis (TB) is a fatal infectious disease; however, the molecular mechanisms underlying the pathogenicity of TB remain elusive. The present study aims to identify potential biomarkers associated with Mycobacterium tuberculosis (M.tb) infection by using integrated bioinformatics and in vitro validation studies. GSE50050, GSE78706, and GSE108844 data from the gene expression omnibus (GEO) database were downloaded to identify differentially expressed genes (DEGs). The functions of DEGs were further subjected to gene ontology (GO) and KEGG pathway analysis. The hub genes from the DEGs were determined based on the protein-protein interaction (PPI) network analysis. Finally, the hub genes were experimentally validated using the in vitro functional studies. A total of 26 common DEGs were identified among GSE50050, GSE78706, and GSE108844. The functional enrichment analysis showed that the common DEGs were associated with cytokines response and TB pathways. The PPI network analysis identified nine hub genes. Further in vitro studies showed that nitric oxide synthase 2 (NOS2) was up-regulated in RAW264.7 cells upon lipopolysaccharides (LPS) stimulation, which was accompanied by increased inflammatory cytokines release. Furthermore, NOS2 was found to be a target of miR-493-5p, which was confirmed by luciferase reporter assay. NOS2 was repressed by miR-493-5p overexpression and was up-regulated after miR-493-5p inhibition in RAW264.7 cells. The rescue experiments showed that LPS-induced increase in the inflammatory cytokines of the RAW264.7 cells was significantly attenuated by NOS2 knockdown and miR-493-5p overexpression. Collectively, our results for the first time demonstrated that NOS2/miR-493-5p signaling pathway may potentially involve in the inflammatory response during bacterial infection such as M. tb infection.
(© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

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