siRNA-Mediated Timp1 Silencing Inhibited the Inflammatory Phenotype during Acute Lung Injury

被引:10
作者
Chernikov, Ivan V. [1 ]
Staroseletz, Yaroslav Yu. [1 ]
Tatarnikova, Irina S. [1 ]
Sen'kova, Aleksandra V. [1 ]
Savin, Innokenty A. [1 ]
Markov, Andrey V. [1 ]
Logashenko, Evgeniya B. [1 ]
Chernolovskaya, Elena L. [1 ]
Zenkova, Marina A. [1 ]
Vlassov, Valentin V. [1 ]
机构
[1] Russian Acad Sci, Inst Chem Biol & Fundamental Med, Siberian Branch, Acad Lavrentiev Ave 8, Novosibirsk 630090, Russia
基金
俄罗斯科学基金会;
关键词
acute lung injury; inflammation; chemically modified siRNA; TIMP1; IL6; LPS; bioinformatics analysis; ACUTE RESPIRATORY-DISTRESS; TISSUE INHIBITOR; MATRIX METALLOPROTEINASES; TARGETING TIMP-1; TNF-ALPHA; DELIVERY; EXPRESSION; LIPOPOLYSACCHARIDE; PATHOGENESIS; ADAM8;
D O I
10.3390/ijms24021641
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
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收藏
页数:27
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