siRNA-Mediated Timp1 Silencing Inhibited the Inflammatory Phenotype during Acute Lung Injury.
Ivan V ChernikovYaroslav Yu StaroseletzIrina S TatarnikovaAleksandra V Sen'kovaInnokenty A SavinArseny D MoralevEvgeniya B LogashenkoElena L ChernolovskayaMarina A ZenkovaValentin V VlassovPublished in: International journal of molecular sciences (2023)
Acute lung injury is a complex cascade process that develops in response to various damaging factors, which can lead to acute respiratory distress syndrome. Within this study, based on bioinformatics reanalysis of available full-transcriptome data of acute lung injury induced in mice and humans by various factors, we selected a set of genes that could serve as good targets for suppressing inflammation in the lung tissue, evaluated their expression in the cells of different origins during LPS-induced inflammation, and chose the tissue inhibitor of metalloproteinase Timp1 as a promising target for suppressing inflammation. We designed an effective chemically modified anti-TIMP1 siRNA and showed that Timp1 silencing correlates with a decrease in the pro-inflammatory cytokine IL6 secretion in cultured macrophage cells and reduces the severity of LPS-induced acute lung injury in a mouse model.
Keyphrases
- lps induced
- inflammatory response
- oxidative stress
- induced apoptosis
- acute respiratory distress syndrome
- mouse model
- cell cycle arrest
- lipopolysaccharide induced
- signaling pathway
- diabetic rats
- extracorporeal membrane oxygenation
- mechanical ventilation
- poor prognosis
- endoplasmic reticulum stress
- gene expression
- cancer therapy
- cell death
- single cell
- adipose tissue
- endothelial cells
- metabolic syndrome
- rna seq
- electronic health record
- transcription factor