Down-regulation of KLF9 ameliorates LPS-caused acute lung injury and inflammation in mice via reducing GSDMD expression.

IF 4.3 3区 材料科学 Q1 ENGINEERING, ELECTRICAL & ELECTRONIC
ACS Applied Electronic Materials Pub Date : 2022-12-01 Epub Date: 2022-08-21 DOI:10.1080/08916934.2022.2114465
Renliang Qu, Jingjing Liu, Lili Feng, Lianbing Li, Junwei Liu, Fengnan Sun, Lin Sun
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引用次数: 5

Abstract

Acute lung injury (ALI) is considered as a severe respiratory disease with aggravated inflammatory responses. Krüppel-like factor 9 (KLF9), a member of KLF family, has been reported to be involved in inflammatory disorders. However, the effect of KLF9 in ALI has not been elucidated. Here the present study was to clarify the role of KLF9 and its mechanism in ALI. The ALI in vitro model was established with lipopolysaccharide (LPS)-treated RAW264.7 cells. Mice were injected with LPS to conduct an ALI in vivo model. The expression of KLF9 and gasdermin D (GSDMD) was examined using quantitative reverse transcription-PCR, haematoxylin-eosin/immunohistochemistry staining and western blot assays. Enzyme-linked immunosorbent assay was employed to detect the levels of inflammatory cytokines. JASPAR database was used to predict the recognition motif of KLF9, and the relationship between KLF9 and GSDMD was determined by luciferase reporter assay and chromatin immunoprecipitation analysis. The number of neutrophils in bronchoalveolar lavage fluid as well as the wet/dry weight ratio was caculated. The results showed that The expression of KLF9 in lung was significantly increased in LPS-stimulated mice. Moreover, KLF9 knockout relieved the lung injury in ALI mice. GSDMD is one of targets genes of the transcription factor KLF9. KLF9 knockout induced a decreased expression of GSDMD in LPS-treated mice. Furthermore, in RAW264.7 cells after LPS administration, KLF9 knockdown reduced the levels of inflammatory factors and suppressed the expression of GSDMD. In summarise, these findings exhibited that KLF9 knockout could mitigate the lung injury and inflammatory responses in ALI mice by directly regulating GSDMD.

下调KLF9可通过降低GSDMD表达改善lps引起的小鼠急性肺损伤和炎症。
急性肺损伤(Acute lung injury, ALI)是一种炎症反应加重的严重呼吸系统疾病。kr ppel样因子9 (KLF9)是KLF家族的一员,据报道与炎症性疾病有关。然而,KLF9在ALI中的作用尚未被阐明。本研究旨在阐明KLF9在ALI中的作用及其机制。采用脂多糖(LPS)处理RAW264.7细胞建立ALI体外模型。小鼠体内注射LPS建立ALI模型。采用定量逆转录- pcr、血红素-伊红/免疫组化染色和western blot检测KLF9和gasdermin D (GSDMD)的表达。采用酶联免疫吸附法检测炎性细胞因子水平。利用JASPAR数据库预测KLF9的识别基序,并通过荧光素酶报告基因测定和染色质免疫沉淀分析确定KLF9与GSDMD的关系。计算支气管肺泡灌洗液中性粒细胞数量及干湿比。结果表明,lps刺激小鼠肺组织中KLF9的表达显著升高。此外,敲除KLF9可减轻ALI小鼠的肺损伤。GSDMD是转录因子KLF9的靶基因之一。敲除KLF9诱导lps处理小鼠GSDMD表达降低。此外,在LPS处理后的RAW264.7细胞中,KLF9敲低可降低炎症因子水平,抑制GSDMD的表达。综上所述,这些发现表明KLF9敲除可以通过直接调节GSDMD来减轻ALI小鼠的肺损伤和炎症反应。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
CiteScore
7.20
自引率
4.30%
发文量
567
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