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Inducing Acute Lung Injury in Mice by Direct Intratracheal Lipopolysaccharide Instillation
Published on: July 6, 2019
MicroRNA-598 inhibition ameliorates LPS-induced acute lung injury in mice through upregulating Ebf1 expression
Qi Zhao1, Lei He2, Junwu Zhang3
1XianYang Vocational Technical College, Tongyi Avenue, Fengxi New Town, Xixian, Xi'an, 712000, Shaanxi, China.
Abstract:
Acute lung injury is a critical acute respiratory distress syndrome (ARDS) with high morbidity and mortality. MicroRNAs (miRNAs) have been demonstrated to play important roles regulating acute lung injury development. In this study, we found that the expression of miR-598 was significantly upregulated in the lung tissues of mice with lipopolysaccharide (LPS)-induced acute lung injury. Both loss-of-function and gain-of-function studies were performed to evaluate the function of miR-598 in acute lung injury. The results showed that inhibition of miR-598 attenuated inflammatory response, oxidative stress, and lung injury in mice treated with LPS, while overexpression of miR-598 exacerbated the LPS-induced acute lung injury. Mechanistically, transcription factor Early B-cell Factor-1 (Ebf1) was predicted and validated as a downstream target of miR-598. Overexpression of Ebf1 attenuated LPS-induced production of inflammatory cytokine TNF-α and IL-6, ameliorated LPS-induced oxidative stress, promoted proliferation, and inhibited apoptosis in murine lung epithelial-15 (MLE-15) cells. Moreover, we demonstrated that Ebf1 knockdown abolished the protective effect of miR-598 inhibition in LPS-treated MLE-15 cells. In summary, miR-598 inhibition ameliorates LPS-induced acute lung injury in mice through upregulating Ebf1 expression, which might provide potential therapeutic treatment for acute lung injury.
Insights
Inhibiting microRNA-598 (miR-598) reduces inflammation and lung injury in acute respiratory distress syndrome (ARDS). Upregulating Early B-cell Factor-1 (Ebf1) mediates this protective effect, offering a potential therapeutic strategy for ARDS.
Area of Science:
- Pulmonary Medicine
- Molecular Biology
- Genetics
Background:
- Acute lung injury (ALI), a severe form of acute respiratory distress syndrome (ARDS), is associated with high morbidity and mortality.
- MicroRNAs (miRNAs) are key regulators in the development of ALI.
- The specific role of miR-598 in ALI pathogenesis remains largely unexplored.
Purpose of the Study:
- To investigate the role of miR-598 in lipopolysaccharide (LPS)-induced acute lung injury.
- To elucidate the underlying molecular mechanisms involving Early B-cell Factor-1 (Ebf1).
- To evaluate the therapeutic potential of targeting miR-598 for ALI treatment.
Main Methods:
- Investigated miR-598 expression in a mouse model of LPS-induced ALI.
- Utilized loss-of-function and gain-of-function studies for miR-598.
- Validated Ebf1 as a direct downstream target of miR-598 using molecular assays.
- Assessed the impact of miR-598 and Ebf1 modulation on inflammatory markers, oxidative stress, and cell viability in lung epithelial cells.
Main Results:
- miR-598 expression was significantly upregulated in LPS-induced ALI lung tissues.
- Inhibition of miR-598 attenuated inflammation, oxidative stress, and lung injury in mice.
- Overexpression of miR-598 exacerbated LPS-induced lung injury.
- Ebf1 was identified as a direct target of miR-598; its overexpression reduced inflammatory cytokines and oxidative stress, promoting cell proliferation and inhibiting apoptosis.
- Ebf1 knockdown abrogated the protective effects of miR-598 inhibition in LPS-treated lung cells.
Conclusions:
- miR-598 plays a critical role in exacerbating LPS-induced acute lung injury.
- Inhibition of miR-598 ameliorates ALI by upregulating Ebf1 expression.
- Targeting the miR-598/Ebf1 pathway presents a promising therapeutic strategy for acute lung injury and ARDS.
