4.4 Article

MicroRNA-139-5p improves sepsis-induced lung injury by targeting Rho-kinase1

期刊

出版社

SPANDIDOS PUBL LTD
DOI: 10.3892/etm.2021.10493

关键词

sepsis; acute lung injury; microRNA; Rho-kinase 1; inflammation; apoptosis

资金

  1. Social Development Projects of Jiangsu Province [BE2017720]

向作者/读者索取更多资源

The study revealed that miR-139-5p alleviated sepsis-induced acute lung injury (ALI) by suppressing its downstream target ROCK1, indicating the promising therapeutic potential of miR-139-5p in treating sepsis-induced ALI.
Sepsis-induced acute lung injury (ALI) is an inflammatory process that involves inflammatory cytokine production and cell apoptosis. In the present study, the regulatory role of microRNA (miR)-139-5p in sepsis-induced ALI was investigated using a murine model of cecal ligation puncture (CLP) and an in vitro model using lipopolysaccharide (LPS)-induced normal human bronchial epithelial cells (NHBEs). Sepsis-induced pathological changes in the lungs of ALI mice were detected using hematoxylin and eosin staining. Lung water content was determined, and the expression of proinflammatory cytokines in the bronchoalveolar lavage fluid and serum of sepsis-induced ALI mice were quantified using ELISA. The levels of oxidative stress in lung tissues were determined using commercial kits. The degree of apoptosis was determined using a TUNEL assay. The expression levels of miR-139-5p and Rho-kinase 1 (ROCK1) were determined using reverse transcription-quantitative PCR and western blot analyses. A dual-luciferase reporter assay was used to confirm the direct targeting of ROCK1 by miR-139-5p. NHBEs were co-transfected with vectors expressing ROCK1 (or empty vector) and miR-139-5p mimics or control mimics prior to LPS treatment. The transcriptional activity of caspase-3, the ratio of apoptotic cells, the expression levels of mucin 5AC, mucin 1, TNF-alpha, IL-1 beta, IL-6, NLR family pyrin domain containing 3, apoptosis-associated speck-like protein containing a CARD and caspase-1 were evaluated. Compared with the normal group, mice that underwent CLP exhibited abnormal lung morphology, enhanced production of TNF-alpha, IL-1 beta and IL-6, increased reactive oxygen species (ROS), malondialdehyde and lactate dehydrogenase levels, an increased proportion of apoptotic cells and increased ROCK1 expression. Superoxide dismutase, glutathione peroxidase and miR-139-5p levels were decreased following CLP. In the NHBEs, stimulation with LPS caused a marked increase in inflammatory cytokine levels and apoptosis compared with the untreated cells. Overexpression of miR-139-5p attenuated cell apoptosis and inflammation. Overexpression of ROCK1 in NHBEs restored the ROS levels and proinflammatory cytokine production inhibited by miR-139-5p. In conclusion, miR-139-5p alleviated sepsis-induced ALI via suppression of its downstream target, ROCK1, suggesting that miR-139-5p may hold promise in the treatment of sepsis-induced ALI.

作者

我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。

评论

主要评分

4.4
评分不足

次要评分

新颖性
-
重要性
-
科学严谨性
-
评价这篇论文

推荐

暂无数据
暂无数据