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Published on: May 21, 2018
miR-122-5p downregulation attenuates lipopolysaccharide-induced acute lung injury by targeting IL1RN
Jie Li1, Xiaoxia Zeng2, Weiqing Wang2
1Department of Pulmonary Disease, Hubei Hospital of Traditional Chinese Medicine, Wuhan, Hubei 430000, P.R. China.
Abstract:
MicroRNAs (miRs) and inflammatory cytokines can induce acute lung injury (ALI), which can develop into acute respiratory distress syndrome in severe cases. Previous research has revealed that miR-122-5p participates in the development of ALI, and that its expression is positively associated with ALI. However, the mechanism by which miR-122-5p contributes to ALI remains to be determined. In the current study, TargetScan and dual luciferase reporter gene assays were used to confirm that IL-1 receptor antagonist (IL1RN) was a target of miR-122-5p. Subsequently, by referring to previous literature, a lipopolysaccharide (LPS)-induced ALI cell model was established. A549 cells were transfected with mimic control or miR-122-5p mimics for 24 h, and 10 µg LPS was used to treat the transfected cells for 12 h. The results revealed that miR-122-5p mimics decreased cell viability and promoted apoptosis. Lactate dehydrogenase (LDH) release assays indicated that miR-122-5p mimics increased LDH release. ELISA demonstrated that miR-122-5p mimics promoted TNF-α, IL-1β and IL-6 expression levels. A549 cells were transfected with inhibitor control, miR-122-5p inhibitor, miR-122-5p inhibitor + control-small interfering (si)RNA or miR-122-5p inhibitor + IL1RN-siRNA for 24 h, after which the cells were treated with 10 µg LPS for 12 h. The results revealed that the effects of the miR-122-5p inhibitor were the opposite of those of the miR-122-5p mimic. All the effects of miR-122-5p inhibitor on LPS-treated A549 cells were significantly reversed by IL1RN-siRNA. Overall, the results highlighted miR-122-5p as a potential novel target for the treatment of ALI.
Insights
MicroRNA-122-5p exacerbates acute lung injury (ALI) by targeting IL-1 receptor antagonist (IL1RN). Inhibiting miR-122-5p shows therapeutic potential for ALI treatment.
Area of Science:
- Pulmonary Medicine
- Molecular Biology
- Cell Biology
Background:
- Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are critical conditions often induced by microRNAs (miRs) and inflammatory cytokines.
- Previous studies indicate miR-122-5p's involvement in ALI pathogenesis, with its expression positively correlating with ALI severity.
- The precise mechanism by which miR-122-5p contributes to ALI progression requires elucidation.
Purpose of the Study:
- To investigate the mechanism underlying miR-122-5p's role in acute lung injury (ALI).
- To identify the direct molecular target of miR-122-5p in the context of ALI.
- To evaluate the therapeutic potential of targeting miR-122-5p for ALI treatment.
Main Methods:
- TargetScan and dual luciferase reporter assays were employed to identify IL-1 receptor antagonist (IL1RN) as a direct target of miR-122-5p.
- A lipopolysaccharide (LPS)-induced ALI cell model using A549 cells was established.
- Cells were transfected with miR-122-5p mimics or inhibitors, followed by LPS treatment, with subsequent assessments of cell viability, apoptosis, lactate dehydrogenase (LDH) release, and inflammatory cytokine levels (TNF-α, IL-1β, IL-6).
- The role of IL1RN was further investigated using small interfering RNA (siRNA) in conjunction with miR-122-5p inhibitors.
Main Results:
- miR-122-5p mimics significantly reduced cell viability, increased apoptosis, and elevated LDH release in LPS-treated A549 cells.
- Overexpression of miR-122-5p promoted the expression of pro-inflammatory cytokines TNF-α, IL-1β, and IL-6.
- Inhibition of miR-122-5p exerted opposite effects, ameliorating LPS-induced cellular damage, and these protective effects were significantly reversed by IL1RN-siRNA, confirming IL1RN's crucial role in the miR-122-5p pathway.
Conclusions:
- IL-1 receptor antagonist (IL1RN) is a direct downstream target of miR-122-5p.
- miR-122-5p promotes LPS-induced acute lung injury (ALI) by negatively regulating IL1RN expression and consequently increasing inflammation and cell damage.
- Targeting miR-122-5p presents a promising therapeutic strategy for managing acute lung injury (ALI).
