Inhibition of miR-21 ameliorates LPS-induced acute lung injury through increasing B cell lymphoma-2 expression

• Published in: Innate immunity (London, England) Vol. 26; no. 8; pp. 693 - 702
• Main Authors: Ge, Junke, Yao, Yanfen, Jia, Haiyan, Li, Pibao, Sun, Wei
• Format: Journal Article
• Language: English
• Published: London, England SAGE Publications 01.11.2020; SAGE PUBLICATIONS, INC; SAGE Publishing
• Subjects: Acute Lung Injury - genetics; Acute Lung Injury - immunology; Alveolar Epithelial Cells - physiology; Alveoli; Animals; Apoptosis; Bcl-2 protein; Cells, Cultured; Cytokines; Epithelial cells; Humans; Inflammation; Inflammation - genetics; Inflammation - immunology; Lipopolysaccharides; Lipopolysaccharides - immunology; Lungs; Lymphoma; Mice; Mice, Inbred BALB C; MicroRNAs - genetics; miRNA; NF-kappa B - metabolism; Original; Overexpression; Permeability; Post-transcription; Proto-Oncogene Proteins c-bcl-2 - genetics; Proto-Oncogene Proteins c-bcl-2 - metabolism; Signal Transduction; Bcl-2; miR-21; mice; ALI; HPAEpiC
• ISSN: 1753-4259; 1753-4267
• DOI: 10.1177/1753425920942574

The aberrant expression of microRNAs (miRNAs) is associated with the pathogenesis of inflammation-related diseases. However, the biological functions of miR-21 in acute lung injury (ALI) remain largely unknown. In this study, the level of miR-21 was obviously increased, but B cell lymphoma-2 (Bcl-2) expression was markedly decreased in LPS-treated human pulmonary alveolar epithelial cells (HPAEpiC). Suppression of miR-21 attenuated LPS-induced apoptosis and inflammation in HPAEpiC and promoted the survival of mice with ALI by decreasing the inflammatory cell count, release of cytokines and permeability in lung tissues. Importantly, Bcl-2 was a direct target of miR-21, and its expression was significantly inhibited by miR-21 mimics at a post-transcriptional level. Besides, Bcl-2 over-expression reversed miR-21-induced apoptosis and inflammation status and showed synergic effects with miR-21 inhibitor in LPS-treated HPAEpiC. In conclusion, inhibition of miR-21 could ameliorate apoptosis and inflammation by restoring the expression of Bcl-2 in LPS-induced HPAEpiC and mice, which might provide therapeutic strategies for the treatment of ALI.