Open Access

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

  • Authors:
    • Xinmin Zhao
    • Mengmeng Wang
    • Zhaorui Sun
    • Suyuan Zhuang
    • Wei Zhang
    • Zhizhou Yang
    • Xiaoqin Han
    • Shinan Nie
  • View Affiliations

  • Published online on: July 26, 2021     https://doi.org/10.3892/etm.2021.10493
  • Article Number: 1059
  • Copyright: © Zhao et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

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‑α, IL‑1β, 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‑α, IL‑1β 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.
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October-2021
Volume 22 Issue 4

Print ISSN: 1792-0981
Online ISSN:1792-1015

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Spandidos Publications style
Zhao X, Wang M, Sun Z, Zhuang S, Zhang W, Yang Z, Han X and Nie S: MicroRNA‑139‑5p improves sepsis‑induced lung injury by targeting Rho‑kinase1. Exp Ther Med 22: 1059, 2021
APA
Zhao, X., Wang, M., Sun, Z., Zhuang, S., Zhang, W., Yang, Z. ... Nie, S. (2021). MicroRNA‑139‑5p improves sepsis‑induced lung injury by targeting Rho‑kinase1. Experimental and Therapeutic Medicine, 22, 1059. https://doi.org/10.3892/etm.2021.10493
MLA
Zhao, X., Wang, M., Sun, Z., Zhuang, S., Zhang, W., Yang, Z., Han, X., Nie, S."MicroRNA‑139‑5p improves sepsis‑induced lung injury by targeting Rho‑kinase1". Experimental and Therapeutic Medicine 22.4 (2021): 1059.
Chicago
Zhao, X., Wang, M., Sun, Z., Zhuang, S., Zhang, W., Yang, Z., Han, X., Nie, S."MicroRNA‑139‑5p improves sepsis‑induced lung injury by targeting Rho‑kinase1". Experimental and Therapeutic Medicine 22, no. 4 (2021): 1059. https://doi.org/10.3892/etm.2021.10493