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MiR-494-3p alleviates acute lung injury through regulating NLRP3 activation by targeting CMPK2
Hong Wang1, Shuqin Wang2, Shanshan Huang2
1Operating Room, Qilu Hospital of Shandong University, Jinan 250012, Shandong, China.
Abstract:
Acute lung injury (ALI) is a severe respiratory disorder with a high rate of mortality, and is characterized by excessive cell apoptosis and inflammation. MicroRNAs (miRNAs) play pivotal roles in ALI. This study examined the biological function of miR-494-3p in cell apoptosis and inflammatory response in ALI. For this, mice were injected with lipopolysaccharide (LPS) to generate an in-vivo model of ALI (ALI mice), and WI-38 cells were stimulated with lipopolysaccharide (LPS) to generate an in-vitro model of ALI. We found that miR-494-3p was significantly downregulated in the ALI mice and in the in-vitro model. Overexpression of miR-494-3p inhibited inflammation and cell apoptosis in the LPS-induced WI-38 cells, and improved the symptoms of lung injury in the ALI mice. We then identified cytidine/uridine monophosphate kinase 2 (CMPK2) as a novel target of miR-494-3p in the WI-38 cells. Furthermore, miR-494-3p suppressed cell apoptosis and the inflammatory response in LPS-treated WI-38 cells through targeting CMPK2. The NLRP3 inflammasome is reportedly responsible for the activation of inflammatory processes. In our study, CMPK2 was confirmed to activate the NLRP3 inflammasome in LPS-treated WI-38 cells. In conclusion, miR-494-3p attenuates ALI through inhibiting cell apoptosis and the inflammatory response by targeting CMPK2, which suggests the value of miR-494-3p as a target for the treatment for ALI.
Insights
MicroRNA-494-3p (miR-494-3p) is downregulated in acute lung injury (ALI). Restoring miR-494-3p levels reduces inflammation and cell death, offering a potential therapeutic target for ALI.
Area of Science:
- Biochemistry
- Molecular Biology
- Immunology
Background:
- Acute lung injury (ALI) is a critical condition with high mortality, marked by inflammation and cell apoptosis.
- MicroRNAs (miRNAs) are implicated in the pathogenesis of ALI.
Purpose of the Study:
- To investigate the role of miR-494-3p in acute lung injury.
- To identify the molecular mechanisms underlying miR-494-3p's function in ALI.
Main Methods:
- Established in-vivo (ALI mice) and in-vitro (LPS-stimulated WI-38 cells) models of ALI.
- Assessed miR-494-3p expression levels.
- Manipulated miR-494-3p expression to evaluate its effects on apoptosis, inflammation, and lung injury.
- Identified and validated CMPK2 as a direct target of miR-494-3p.
- Investigated the role of CMPK2 in NLRP3 inflammasome activation.
Main Results:
- miR-494-3p expression was significantly decreased in ALI models.
- Overexpression of miR-494-3p attenuated inflammation and cell apoptosis in vitro and improved lung injury in vivo.
- Cytidine/uridine monophosphate kinase 2 (CMPK2) was identified as a direct target of miR-494-3p.
- miR-494-3p inhibited apoptosis and inflammation by targeting CMPK2.
- CMPK2 was shown to activate the NLRP3 inflammasome in LPS-treated cells.
Conclusions:
- miR-494-3p plays a protective role in ALI by suppressing cell apoptosis and inflammation.
- The therapeutic effect of miR-494-3p in ALI is mediated through the inhibition of CMPK2 and subsequent NLRP3 inflammasome activation.
- miR-494-3p represents a promising therapeutic target for the treatment of acute lung injury.
