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Updated: Jul 18, 2025
Mouse Model of Oleic Acid-Induced Acute Respiratory Distress Syndrome
Published on: June 2, 2022
miR-346 regulates the development of ARDS by regulating the function of pulmonary microvascular endothelial cells
Jing Jiang1, Fei Guo2, Wei Li1
1Department of Pulmonary and Critical Care Medicine, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, Shandong, 264000, China.
Abstract:
In recent years, many studies have reported that microRNAs play an important role in the pathogenesis of a variety of diseases, and the aim of this paper is to explore the role and mechanism of miR-346 in acute respiratory distress syndrome (ARDS). A mouse model of ARDS was constructed by LPS induction, and RT-qPCR assay was used to verify that the expression level of miR-346 in lung tissue was significantly increased, and was negatively correlated with oxygenation index. Inhibiting the expression of miR-346 in mice and HPMECs by miR-346 inhibitor confirmed that decreased miR-346 expression could lead to increased oxygenation index, decreased lung index, lung water content and NO content to reduce lung injury in mice, while lung inflammation was alleviated and apoptosis was reduced in mice. The same results were obtained in cells. BCL6 was predicted to be a target of miR-346 by targetscan and miRDB; when miR-346 was inhibited, BCL6 expression was increased, and if miR-346 and BCL6 expression were inhibited at the same time, it could aggravate lung injury and reduce the proliferation of HPMECs and increase their apoptosis and inflammation in mice. This shows that miR-346 inhibits the migration of HPMECs by regulating BCL6 expression, which in turn promotes the apoptosis of HPMECs, leading to inflammation and inducing ARDS.
Insights
MicroRNA-346 (miR-346) exacerbates acute respiratory distress syndrome (ARDS) by promoting lung inflammation and cell apoptosis. Inhibiting miR-346 alleviates lung injury, suggesting it as a therapeutic target for ARDS.
Area of Science:
- Molecular Biology
- Respiratory Medicine
- Pathogenesis Research
Background:
- MicroRNAs (miRNAs) are increasingly recognized for their roles in disease development.
- The specific involvement of miR-346 in acute respiratory distress syndrome (ARDS) remains to be fully elucidated.
- Understanding miRNA mechanisms is crucial for developing novel therapeutic strategies for ARDS.
Purpose of the Study:
- To investigate the role and underlying mechanism of miR-346 in the pathogenesis of ARDS.
- To determine the relationship between miR-346 expression levels and ARDS severity.
- To identify potential molecular targets of miR-346 involved in ARDS.
Main Methods:
- Establishment of a lipopolysaccharide (LPS)-induced mouse model of ARDS.
- Quantitative reverse transcription polymerase chain reaction (RT-qPCR) to measure miR-346 expression.
- Inhibition of miR-346 in vivo and in vitro (HPMECs) using miR-346 inhibitors.
- Bioinformatic prediction and experimental validation of miR-346 targets (BCL6).
Main Results:
- miR-346 expression was significantly upregulated in the lungs of ARDS mice and negatively correlated with the oxygenation index.
- Inhibition of miR-346 reduced lung injury markers (lung index, lung water content, NO), alleviated inflammation, and decreased apoptosis.
- BCL6 was identified as a target of miR-346; simultaneous inhibition of miR-346 and BCL6 exacerbated lung injury and HPMEC dysfunction.
Conclusions:
- miR-346 plays a pro-inflammatory and pro-apoptotic role in ARDS pathogenesis.
- miR-346 promotes ARDS by inhibiting HPMEC migration via BCL6 regulation, leading to increased apoptosis and inflammation.
- Targeting miR-346 presents a potential therapeutic strategy for mitigating ARDS.
