The function and mechanism of microRNA-92a-3p in lipopolysaccharide-induced acute lung injury

• Published in: Immunopharmacology and immunotoxicology 2022-01, Vol.44 (1), p.47-57
• Main Authors: Wang, Cong, Li, Yang-Hao, Yang, Ze-Tian, Cheng, Ni-Tao, Tang, He-Xiao, Xu, Ming
• Format: Article
• Language: English
• Subjects: Acute Lung Injury - chemically induced; Acute Lung Injury - genetics; Acute Lung Injury - metabolism; AKAP1; ALI; Animals; Lipopolysaccharides - toxicity; LPS; Mice; MicroRNAs - genetics; MicroRNAs - metabolism; miR-92a-3p; Oxidative Stress; Sepsis
• ISSN: 0892-3973; 1532-2513
• DOI: 10.1080/08923973.2021.2001497

Sepsis-associated acute lung injury (ALI) is a clinically severe respiratory disorder and remains the leading cause of multiple organ failure and mortality. Herein, we used lipopolysaccharide (LPS) to generate sepsis-induced ALI and try to explore the role and mechanism of microRNA-92a-3p (miR-92a-3p) in this process. Mice were intravenously injected with miR-92a-3p agomir, antagomir and negative controls for 3 consecutive days and then were intratracheally instillated by LPS (5 mg/kg) for 12 h. To knock down the endogenous A-kinase anchoring protein 1 (AKAP1), mice were intratracheally injected with recombinant adenovirus carrying the short hairpin RNA targeting AKAP1 (shAkap1) at 1 week before LPS administration. miR-92a-3p level was significantly upregulated in the lungs by LPS injection. miR-92a-3p antagomir reduced LPS-induced intrapulmonary inflammation and oxidative stress, thereby preventing pulmonary injury and dysfunction. In contrast, miR-92a-3p agomir aggravated LPS-induced intrapulmonary inflammation, oxidative stress, pulmonary injury and dysfunction. Moreover, we reported that AKAP1 upregulation was required for the beneficial effects of miR-92a-3p antagomir, and that AKAP1 knockdown completely abolished the anti-inflammatory and antioxidant capacities of miR-92a-3p antagomir. Our data identify that miR-92a-3p modulates LPS-induced intrapulmonary inflammation, oxidative stress and ALI via AKAP1 in mice.