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

来源：

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES | 2023年 / 24卷 / 02期

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.

引用

页数：27

共 132 条

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