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Downregulated microRNA-27b attenuates lipopolysaccharide-induced acute lung injury via activation of NF-E2-related factor 2 and inhibition of nuclear factor κB signaling pathway.
J Cell Physiol. 2019 05; 234(5):6023-6032.JC

Abstract

Acute lung injury (ALI) is a life-threatening, diffuse heterogeneous lung injury characterized by acute onset, pulmonary edema, and respiratory failure. Lipopolysaccharide (LPS) is a leading cause for ALI and when administered to a mouse it induces a lung phenotype exhibiting some of the clinical characteristics of human ALI. This study focused on investigating whether microRNA-27b (miR-27b) affects ALI in a mouse model established by LPS-induction and to further explore the underlying mechanism. After model establishment, the mice were treated with miR-27b agomir, miR-27b antagomir, or D-ribofuranosylbenzimidazole (an inhibitor of nuclear factor-E2-related factor 2 [Nrf2]) to determine levels of miR-27b, Nrf2, nuclear factor kappa-light-chain-enhancer of activated B cells nuclear factor κB (NF-κB), p-NF-κB, and heme oxygenase-1 (HO-1). The levels of interleukin (IL)-1β, IL-6, and tumor necrosis factor-α (TNF-α) in bronchoalveolar lavage fluid (BALF) were determined. The results of luciferase activity suggested that Nrf2 was a target gene of miR-27b. It was indicated that the Nrf2 level decreased in lung tissues from ALI mice. The downregulation of miR-27b decreased the levels of IL-1β, IL-6, and TNF-α in BALF of ALI mice. Downregulated miR-27b increased Nrf2 level, thus enhancing HO-1 level along with reduction of NF-κB level as well as the extent of NF-κB phosphorylation in the lung tissues of the transfected mice. Pathological changes were ameliorated in LPS-reduced mice elicited by miR-27b inhibition. The results of this study demonstrate that downregulated miR-27b couldenhance Nrf2 and HO-1 expressions, inhibit NF-κB signaling pathway, which exerts a protective effect on LPS-induced ALI in mice.

Authors+Show Affiliations

Department of Pulmonary and Critical Care Medicine, Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing, China.Department of Pulmonary and Critical Care Medicine, Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing, China.Department of Pulmonary and Critical Care Medicine, Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing, China.Department of Pulmonary and Critical Care Medicine, Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing, China.Department of Pulmonary and Critical Care Medicine, Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing, China.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

30584668

Citation

Huang, Yan, et al. "Downregulated microRNA-27b Attenuates Lipopolysaccharide-induced Acute Lung Injury Via Activation of NF-E2-related Factor 2 and Inhibition of Nuclear Factor κB Signaling Pathway." Journal of Cellular Physiology, vol. 234, no. 5, 2019, pp. 6023-6032.
Huang Y, Huang L, Zhu G, et al. Downregulated microRNA-27b attenuates lipopolysaccharide-induced acute lung injury via activation of NF-E2-related factor 2 and inhibition of nuclear factor κB signaling pathway. J Cell Physiol. 2019;234(5):6023-6032.
Huang, Y., Huang, L., Zhu, G., Pei, Z., & Zhang, W. (2019). Downregulated microRNA-27b attenuates lipopolysaccharide-induced acute lung injury via activation of NF-E2-related factor 2 and inhibition of nuclear factor κB signaling pathway. Journal of Cellular Physiology, 234(5), 6023-6032. https://doi.org/10.1002/jcp.27187
Huang Y, et al. Downregulated microRNA-27b Attenuates Lipopolysaccharide-induced Acute Lung Injury Via Activation of NF-E2-related Factor 2 and Inhibition of Nuclear Factor κB Signaling Pathway. J Cell Physiol. 2019;234(5):6023-6032. PubMed PMID: 30584668.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Downregulated microRNA-27b attenuates lipopolysaccharide-induced acute lung injury via activation of NF-E2-related factor 2 and inhibition of nuclear factor κB signaling pathway. AU - Huang,Yan, AU - Huang,Lixue, AU - Zhu,Guangfa, AU - Pei,Zhenye, AU - Zhang,Wenmei, Y1 - 2018/12/24/ PY - 2018/02/25/received PY - 2018/07/17/accepted PY - 2018/12/26/pubmed PY - 2020/3/31/medline PY - 2018/12/26/entrez KW - NF-E2-related factor 2 (Nrf2) KW - acute lung injury (ALI) KW - lipopolysaccharide (LPS) KW - microRNA-27b (miRNA-27b) KW - nuclear factor κB (NK-κB) signaling pathway SP - 6023 EP - 6032 JF - Journal of cellular physiology JO - J Cell Physiol VL - 234 IS - 5 N2 - Acute lung injury (ALI) is a life-threatening, diffuse heterogeneous lung injury characterized by acute onset, pulmonary edema, and respiratory failure. Lipopolysaccharide (LPS) is a leading cause for ALI and when administered to a mouse it induces a lung phenotype exhibiting some of the clinical characteristics of human ALI. This study focused on investigating whether microRNA-27b (miR-27b) affects ALI in a mouse model established by LPS-induction and to further explore the underlying mechanism. After model establishment, the mice were treated with miR-27b agomir, miR-27b antagomir, or D-ribofuranosylbenzimidazole (an inhibitor of nuclear factor-E2-related factor 2 [Nrf2]) to determine levels of miR-27b, Nrf2, nuclear factor kappa-light-chain-enhancer of activated B cells nuclear factor κB (NF-κB), p-NF-κB, and heme oxygenase-1 (HO-1). The levels of interleukin (IL)-1β, IL-6, and tumor necrosis factor-α (TNF-α) in bronchoalveolar lavage fluid (BALF) were determined. The results of luciferase activity suggested that Nrf2 was a target gene of miR-27b. It was indicated that the Nrf2 level decreased in lung tissues from ALI mice. The downregulation of miR-27b decreased the levels of IL-1β, IL-6, and TNF-α in BALF of ALI mice. Downregulated miR-27b increased Nrf2 level, thus enhancing HO-1 level along with reduction of NF-κB level as well as the extent of NF-κB phosphorylation in the lung tissues of the transfected mice. Pathological changes were ameliorated in LPS-reduced mice elicited by miR-27b inhibition. The results of this study demonstrate that downregulated miR-27b couldenhance Nrf2 and HO-1 expressions, inhibit NF-κB signaling pathway, which exerts a protective effect on LPS-induced ALI in mice. SN - 1097-4652 UR - https://www.unboundmedicine.com/medline/citation/30584668/Downregulated_microRNA_27b_attenuates_lipopolysaccharide_induced_acute_lung_injury_via_activation_of_NF_E2_related_factor_2_and_inhibition_of_nuclear_factor_κB_signaling_pathway_ L2 - https://doi.org/10.1002/jcp.27187 DB - PRIME DP - Unbound Medicine ER -