MicroRNA-144-3p enhances LPS induced septic acute lung injury in mice through downregulating Caveolin-2

• Published in: Immunology letters 2021-03, Vol.231, p.18-25
• Main Authors: Xu, Ruiming, Shao, Zhengyi, Cao, Qiumei
• Format: Article
• Language: English
• Subjects: Animals; Biomarkers; Caveolin 2 - genetics; Caveolin-2; Cytokines - metabolism; Disease Models, Animal; Disease Susceptibility; Gene Expression Regulation; Immunohistochemistry; Inflammation Mediators - metabolism; JAK/STAT signal pathway; Janus Kinases - metabolism; Lipopolysaccharides - adverse effects; LPS; Male; Mice; MicroRNAs - genetics; miR-144-3p; RNA Interference; Sepsis - diagnosis; Sepsis - etiology; Sepsis - metabolism; Septic acute lung injury; Signal Transduction; STAT Transcription Factors - metabolism
• ISSN: 0165-2478; 1879-0542
• DOI: 10.1016/j.imlet.2020.12.015

•Ectopic expressions of miR-144-3p and Caveolin-2 in septic ALI.•miR-144-3p facilitates inflammation and apoptosis in LPS induced ALI.•Caveolin-2 suppresses the progression of septic ALI.•Caveolin-2 is a target gene of miR-144-3p. The emphasis of this study focused on the possible implication and the mechanism of miR-144−3p in septic acute lung injury (ALI) condition. Mice were pre-injected with miR-144−3p agomir, miR-144−3p antagomir, sh-Caveolin-2 or PBS before 10 mg/kg LPS induced sepsis model establishment. The ratio of wet weight of lung tissues and body weight (W/W) was calculated. The pathological changes on lung tissues were observed by H&E staining. Secretions of inflammatory cytokines (TNF-α, IL-1β and IL-6) in both mouse serum and lung tissues were determined by ELISA. Cell apoptosis and cell morphology were measured by TUNEL staining and H&E staining. The expressions of miR-144−3p, Caveolin-2, apoptotic related proteins and JAK/STAT pathway related proteins were measured by qRT-PCR or/and Western blot. Dual luciferase reporter assay was applied to detect the binding of miR-144−3p with Caveolin-2. LPS resulted in increased W/W, disrupted lung tissue, enhanced inflammatory response and cell apoptosis. miR-144−3p was upregulated while Caveolin-2 was downregulated in response to LPS treatment. Inflammation and cell apoptosis induced by LPS can be alleviated by miR-144−3p antagomir injection, but enhanced by miR-144−3p agomir or sh-Caveolin-2 treatment. miR-144−3p can negatively target Caveolin-2. miR-144−3p can activate the JAK/STAT signal pathway through Caveolin-2 in septic ALI mouse. miR-144−3 can promote LPS induced septic ALI through downregulating Caveolin-2 to activate the JAK/STAT signal pathway.